198 results on '"Muriel T. Davisson"'
Search Results
2. Love at First Site
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Muriel T. Davisson
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Biology (General) ,QH301-705.5 - Published
- 2003
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3. Classification of mouse chromosomes using artificial neural networks.
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Mohamad T. Musavi, M. Qiao, Muriel T. Davisson, and E. C. Akeson
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- 1996
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4. The Mouse Genome Database (MGD): expanding genetic and genomic resources for the laboratory mouse.
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Judith A. Blake, Janan T. Eppig, Joel E. Richardson, and Muriel T. Davisson
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- 2000
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5. The Mouse Genome Database (MGD): genetic and genomic information about the laboratory mouse. The Mouse Genome Database Group.
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Judith A. Blake, Joel E. Richardson, Muriel T. Davisson, and Janan T. Eppig
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- 1999
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6. The Mouse Genome Database (MGD): a community resource. Status and enhancements. The Mouse Genome Informatics Group.
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Judith A. Blake, Janan T. Eppig, Joel E. Richardson, and Muriel T. Davisson
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- 1998
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7. Mouse chromosome classification by radial basis function network with fast orthogonal search.
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Mohamad T. Musavi, Ronald J. Bryant, M. Qiao, Muriel T. Davisson, E. C. Akeson, and B. D. French
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- 1998
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8. The Mouse Genome Database (MGD). A comprehensive public resource of genetic, phenotypic and genomic data. The Mouse Genome Informatics Group.
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Judith A. Blake, Joel E. Richardson, Muriel T. Davisson, and Janan T. Eppig
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- 1997
- Full Text
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9. The Jackson Laboratory Mouse Mutant Resource
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Muriel T. Davisson
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Genetics ,Resource (biology) ,Mutant ,Laboratory mouse ,Biology - Published
- 2020
10. A spontaneous mutation in contactin 1 in the mouse.
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Muriel T Davisson, Roderick T Bronson, Abigail L D Tadenev, William W Motley, Arjun Krishnaswamy, Kevin L Seburn, and Robert W Burgess
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Medicine ,Science - Abstract
Mutations in the gene encoding the immunoglobulin-superfamily member cell adhesion molecule contactin1 (CNTN1) cause lethal congenital myopathy in human patients and neurodevelopmental phenotypes in knockout mice. Whether the mutant mice provide an accurate model of the human disease is unclear; resolving this will require additional functional tests of the neuromuscular system and examination of Cntn1 mutations on different genetic backgrounds that may influence the phenotype. Toward these ends, we have analyzed a new, spontaneous mutation in the mouse Cntn1 gene that arose in a BALB/c genetic background. The overt phenotype is very similar to the knockout of Cntn1, with affected animals having reduced body weight, a failure to thrive, locomotor abnormalities, and a lifespan of 2-3 weeks. Mice homozygous for the new allele have CNTN1 protein undetectable by western blotting, suggesting that it is a null or very severe hypomorph. In an analysis of neuromuscular function, neuromuscular junctions had normal morphology, consistent with previous studies in knockout mice, and the muscles were able to generate appropriate force when normalized for their reduced size in late stage animals. Therefore, the Cntn1 mutant mice do not show evidence for a myopathy, but instead the phenotype is likely to be caused by dysfunction in the nervous system. Given the similarity of CNTN1 to other Ig-superfamily proteins such as DSCAMs, we also characterized the expression and localization of Cntn1 in the retinas of mutant mice for developmental defects. Despite widespread expression, no anomalies in retinal anatomy were detected histologically or using a battery of cell-type specific antibodies. We therefore conclude that the phenotype of the Cntn1 mice arises from dysfunction in the brain, spinal cord or peripheral nervous system, and is similar in either a BALB/c or B6;129;Black Swiss background, raising a possible discordance between the mouse and human phenotypes resulting from Cntn1 mutations.
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- 2011
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11. Age exacerbates abnormal protein expression in a mouse model of Down syndrome
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Suhong Tong, Muriel T. Davisson, Katheleen Gardiner, Aaron Block, and Md. Mahiuddin Ahmed
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Male ,0301 basic medicine ,Aging ,Cerebellum ,Down syndrome ,Basal Forebrain ,Chromosomes, Human, Pair 21 ,Gene Expression ,Nerve Tissue Proteins ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Memory ,medicine ,Animals ,Humans ,Learning ,Cholinergic neuron ,Protein kinase A ,Mechanistic target of rapamycin ,Mice, Inbred C3H ,Basal forebrain ,General Neuroscience ,medicine.disease ,Cholinergic Neurons ,Cortex (botany) ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Female ,Neurology (clinical) ,Down Syndrome ,Geriatrics and Gerontology ,Chromosome 21 ,Neuroscience ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non–human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease. Among brain regions, the number of abnormalities in cerebellum decreased while the number in cortex greatly increased with age. The Ts65Dn is being used in preclinical evaluations of drugs for cognition in DS. Most commonly, drug evaluations are tested in ∼4- to 6-month-old mice. Data on age-related changes in magnitude and specificity of protein perturbations can be used to understand the molecular basis of changes in cognitive ability and to predict potential age-related specificities in drug efficacies.
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- 2017
12. A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen α3α4α5(IV) trimers
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Roderick T. Bronson, Ron Korstanje, Christina R. Caputo, Rosalinda A Doty, Susan A. Cook, Muriel T. Davisson, and Jeffrey H. Miner
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Collagen Type IV ,Male ,Mice, 129 Strain ,Time Factors ,Interstitial nephritis ,Mutant ,Nephritis, Hereditary ,Biology ,urologic and male genital diseases ,medicine.disease_cause ,Autoantigens ,Article ,Exon ,Glomerular Basement Membrane ,medicine ,Albuminuria ,Animals ,Genetic Predisposition to Disease ,RNA, Messenger ,Alport syndrome ,Mutation ,Glomerular basement membrane ,Glomerulosclerosis ,medicine.disease ,Molecular biology ,Disease Models, Animal ,Phenotype ,medicine.anatomical_structure ,Gene Expression Regulation ,Mice, Inbred DBA ,Nephrology ,Immunology ,Female ,Protein Multimerization ,Nephritis - Abstract
A spontaneous mutation termed bilateral wasting kidneys ( bwk ) was identified in a colony of NONcNZO recombinant inbred mice. These mice exhibit a rapid increase of urinary albumin at an early age associated with glomerulosclerosis, interstitial nephritis, and tubular atrophy. The mutation was mapped to a location on chromosome 1 containing the Col4a3 and Col4a4 genes, for which mutations in the human orthologs cause the hereditary nephritis Alport syndrome. DNA sequencing identified a G-to-A mutation in the conserved GT splice donor of Col4a4 intron 30, resulting in skipping of exon 30 but maintaining the mRNA reading frame. Protein analyses showed that mutant collagen α3α4α5(IV) trimers were secreted and incorporated into the glomerular basement membrane (GBM), but levels were low, and GBM lesions typical of Alport syndrome were observed. Moving the mutation into the more renal damage–prone DBA/2J and 129S1/SvImJ backgrounds revealed differences in albuminuria and its rate of increase, suggesting an interaction between the Col4a4 mutation and modifier genes. This novel mouse model of Alport syndrome is the only one shown to accumulate abnormal collagen α3α4α5(IV) in the GBM, as also found in a subset of Alport patients. These mice will be valuable for testing potential therapies, for understanding abnormal collagen IV structure and assembly, and for gaining better insights into the mechanisms leading to Alport syndrome, and to the variability in the age of onset and associated phenotypes.
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- 2014
13. A mouse model for Down syndrome exhibits learning and behaviour deficits
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Roderick T. Bronson, Cheryl A. Kitt, Anny Wohn, Roger H. Reeves, Sangram S. Sisodia, N.G. Irving, Cecilia Schmidt, Muriel T. Davisson, and Timothy H. Moran
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Male ,Down syndrome ,Chromosomes, Human, Pair 21 ,Aneuploidy ,Gene Expression ,Biology ,Motor Activity ,Mice ,Mice, Neurologic Mutants ,Chromosome 16 ,Alzheimer Disease ,Genetics ,medicine ,Animals ,Humans ,Learning ,Gene ,Analysis of Variance ,Mice, Inbred C3H ,Sex Characteristics ,Amyloid beta-Peptides ,Trisomy 16 ,Chromosome Mapping ,medicine.disease ,Phenotype ,Mice, Inbred C57BL ,Disease Models, Animal ,Female ,Alzheimer's disease ,Down Syndrome ,Trisomy - Abstract
Trisomy 21 or Down syndrome (DS) is the most frequent genetic cause of mental retardation, affecting one in 800 live born human beings. Mice with segmental trisomy 16 (Ts65Dn mice) are at dosage imbalance for genes corresponding to those on human chromosome 21q21-22.3--which includes the so-called DS 'critical region'. They do not show early-onset of Alzheimer disease pathology; however, Ts65Dn mice do demonstrate impaired performance in a complex learning task requiring the integration of visual and spatial information. The reproducibility of this phenotype among Ts65Dn mice indicates that dosage imbalance for a gene or genes in this region contributes to this impairment. The corresponding dosage imbalance for the human homologues of these genes may contribute to cognitive deficits in DS.
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- 2016
14. Loss of Correlations among Proteins in Brains of the Ts65Dn Mouse Model of Down Syndrome
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Xiaolu Sturgeon, Md. Mahiuddin Ahmed, Katheleen Gardiner, Misoo Ellison, and Muriel T. Davisson
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Male ,Down syndrome ,Cerebellum ,Proteome ,Blotting, Western ,Protein Array Analysis ,Hippocampus ,Mice, Transgenic ,Nerve Tissue Proteins ,Biology ,Receptors, N-Methyl-D-Aspartate ,Biochemistry ,Mice ,medicine ,Animals ,Protein Interaction Maps ,Extracellular Signal-Regulated MAP Kinases ,Gene ,Brain Chemistry ,Genetics ,Brain ,Reproducibility of Results ,General Chemistry ,medicine.disease ,Phenotype ,Disease Models, Animal ,medicine.anatomical_structure ,Female ,Down Syndrome ,Trisomy ,Chromosome 21 - Abstract
The Ts65Dn mouse model of Down syndrome (DS) is trisomic for orthologs of 88 of 161 classical protein coding genes present on human chromosome 21 (HSA21). Ts65Dn mice display learning and memory impairments and neuroanatomical, electrophysiological, and cellular abnormalities that are relevant to phenotypic features seen in DS; however, little is known about the molecular perturbations underlying the abnormalities. Here we have used reverse phase protein arrays to profile 64 proteins in the cortex, hippocampus, and cerebellum of Ts65Dn mice and littermate controls. Proteins were chosen to sample a variety of pathways and processes and include orthologs of HSA21 proteins and phosphorylation-dependent and -independent forms of non-HSA21 proteins. Protein profiles overall show remarkable stability to the effects of trisomy, with fewer than 30% of proteins altered in any brain region. However, phospho-proteins are less resistant to trisomy than their phospho-independent forms, and Ts65Dn display abnormalities in some key proteins. Importantly, we demonstrate that Ts65Dn mice have lost correlations seen in control mice among levels of functionally related proteins, including components of the MAP kinase pathway and subunits of the NMDA receptor. Loss of normal patterns of correlations may compromise molecular responses to stimulation and underlie deficits in learning and memory.
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- 2012
15. Otitis media in a mouse model for Down syndrome
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Jiangping Zhang, Cong Tian, Casey Nava, Qing Yin Zheng, Fengchan Han, Heping Yu, Muriel T. Davisson, and Cecilia Schmidt
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Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Down syndrome ,Pathology ,medicine.medical_specialty ,Hearing loss ,animal diseases ,Hearing Loss, Conductive ,Ear, Middle ,Trisomy ,Opportunistic Infections ,Biology ,Pathology and Forensic Medicine ,Mice ,mental disorders ,Evoked Potentials, Auditory, Brain Stem ,otorhinolaryngologic diseases ,medicine ,Animals ,Molecular Biology ,Otitis Media with Effusion ,Bacterial Infections ,Original Articles ,Cell Biology ,medicine.disease ,Mice, Mutant Strains ,Disease Models, Animal ,Otitis ,medicine.anatomical_structure ,Auditory brainstem response ,Effusion ,Sensory Thresholds ,Middle ear ,sense organs ,Brainstem ,Down Syndrome ,medicine.symptom - Abstract
The Ts65Dn mouse shares many phenotypic characteristics of human Down syndrome. Here, we report that otitis media, characterized by effusion in the middle ear and hearing loss, was prevalent in Ts65Dn mice. Of the 53 Ts65Dn mice tested, 81.1% had high auditory-evoked brainstem response (ABR) thresholds for at least one of the stimulus frequencies (click, 8 kHz, 16 kHz and 32 kHz), in at least one ear. The ABR thresholds were variable and showed no tendency toward increase with age, from 2 to 7 months of age. Observation of pathology in mice, aged 3–4 months, revealed middle ear effusion in 11 of 15 Ts65Dn mice examined, but only in two of 11 wild-type mice. The effusion in each mouse varied substantially in volume and inflammatory cell content. The middle ear mucosae were generally thickened and goblet cells were distributed with higher density in the epithelium of the middle ear cavity of Ts65Dn mice as compared with those of wild-type controls. Bacteria of pathogenic importance to humans also were identified in the Ts65Dn mice. This is the first report of otitis media in the Ts65Dn mouse as a model characteristic of human Down syndrome.
- Published
- 2009
16. VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P2 in yeast and mouse
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Sujin Park, Yanling Zhang, Dan Goldowitz, Li Liu, Natsuko Jin, Muriel T. Davisson, Miriam H. Meisler, Clement Y. Chow, Roderick T. Bronson, Jason E. Duex, Jason L. Petersen, Lois S. Weisman, and Sergey N. Zolov
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0303 health sciences ,Mutation ,Phosphatidylinositol 3,5-bisphosphate ,General Immunology and Microbiology ,biology ,Endosome ,General Neuroscience ,Saccharomyces cerevisiae ,Mutant ,Plasma protein binding ,medicine.disease_cause ,biology.organism_classification ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,PIKFYVE ,chemistry.chemical_compound ,0302 clinical medicine ,Biochemistry ,chemistry ,Pi ,medicine ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
The signalling lipid PI(3,5)P2 is generated on endosomes and regulates retrograde traffic to the trans-Golgi network. Physiological signals regulate rapid, transient changes in PI(3,5)P2 levels. Mutations that lower PI(3,5)P2 cause neurodegeneration in human patients and mice. The function of Vac14 in the regulation of PI(3,5)P2 was uncharacterized previously. Here, we predict that yeast and mammalian Vac14 are composed entirely of HEAT repeats and demonstrate that Vac14 exerts an effect as a scaffold for the PI(3,5)P2 regulatory complex by direct contact with the known regulators of PI(3,5)P2: Fig4, Fab1, Vac7 and Atg18. We also report that the mouse mutant ingls (infantile gliosis) results from a missense mutation in Vac14 that prevents the association of Vac14 with Fab1, generating a partial complex. Analysis of ingls and two additional mutants provides insight into the organization of the PI(3,5)P2 regulatory complex and indicates that Vac14 mediates three distinct mechanisms for the rapid interconversion of PI3P and PI(3,5)P2. Moreover, these studies show that the association of Fab1 with the complex is essential for viability in the mouse.
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- 2008
17. Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome
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Gilbert Di Paolo, Laurent Cimasoni, Samuel G. Frere, Markus R. Wenk, Silvia Giovedì, Elizabeth A. Pollina, Hong Zhang, Ottavio Arancio, Katheleen Gardiner, Sergey V. Voronov, Pietro De Camilli, Cecilia Schmidt, Stylianos E. Antonarakis, Christelle Borel, Muriel T. Davisson, and Ellen C. Akeson
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Male ,Phosphatidylinositol 4,5-Diphosphate ,Genetically modified mouse ,Transgene ,Phosphatase ,Gene Dosage ,Morris water navigation task ,Mice, Transgenic ,Nerve Tissue Proteins ,Neurotransmission ,Biology ,Gene dosage ,Synapse ,Phosphoric Monoester Hydrolases/genetics/ metabolism ,Mice ,Cognition Disorders/ enzymology ,Animals ,Homeostasis ,Learning ,Maze Learning ,Brain/enzymology/pathology ,ddc:616 ,Genetics ,Multidisciplinary ,Brain ,Biological Sciences ,Nerve Tissue Proteins/genetics/ metabolism ,Phosphoric Monoester Hydrolases ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,Down Syndrome/ enzymology ,Down Syndrome ,Phosphatidylinositol 4,5-Diphosphate/ metabolism ,Cognition Disorders ,Chromosome 21 - Abstract
Phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2 ] is a signaling phospholipid implicated in a wide variety of cellular functions. At synapses, where normal PtdIns(4,5)P 2 balance is required for proper neurotransmission, the phosphoinositide phosphatase synaptojanin 1 is a key regulator of its metabolism. The underlying gene, SYNJ1 , maps to human chromosome 21 and is thus a candidate for involvement in Down's syndrome (DS), a complex disorder resulting from the overexpression of trisomic genes. Here, we show that PtdIns(4,5)P 2 metabolism is altered in the brain of Ts65Dn mice, the most commonly used model of DS. This defect is rescued by restoring Synj1 to disomy in Ts65Dn mice and is recapitulated in transgenic mice overexpressing Synj1 from BAC constructs. These transgenic mice also exhibit deficits in performance of the Morris water maze task, suggesting that PtdIns(4,5)P 2 dyshomeostasis caused by gene dosage imbalance for Synj1 may contribute to brain dysfunction and cognitive disabilities in DS.
- Published
- 2008
18. Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration
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Susan A. Cook, Muriel T. Davisson, Chantal M. Longo-Guess, John P. Sundberg, Paul Schimmel, Jeong Woong Lee, Jaeseon Jang, Kirk Beebe, Susan L. Ackerman, and Leslie A. Nangle
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Models, Molecular ,Protein Folding ,Molecular Sequence Data ,RNA, Transfer, Ala ,Cerebellar Purkinje cell ,Biology ,medicine.disease_cause ,Catalysis ,Mice ,Purkinje Cells ,JUNQ and IPOD ,Escherichia coli ,Serine ,medicine ,Animals ,Humans ,Mutation ,Alanine ,Multidisciplinary ,Alanine-tRNA Ligase ,Neurodegeneration ,Acetylation ,Neurodegenerative Diseases ,Fibroblasts ,medicine.disease ,Mice, Mutant Strains ,Protein Structure, Tertiary ,Mice, Inbred C57BL ,Phenotype ,Aggresome ,Biochemistry ,Transfer RNA ,Unfolded protein response ,Protein folding - Abstract
Misfolded proteins are associated with several pathological conditions including neurodegeneration. Although some of these abnormally folded proteins result from mutations in genes encoding disease-associated proteins (for example, repeat-expansion diseases), more general mechanisms that lead to misfolded proteins in neurons remain largely unknown. Here we demonstrate that low levels of mischarged transfer RNAs (tRNAs) can lead to an intracellular accumulation of misfolded proteins in neurons. These accumulations are accompanied by upregulation of cytoplasmic protein chaperones and by induction of the unfolded protein response. We report that the mouse sticky mutation, which causes cerebellar Purkinje cell loss and ataxia, is a missense mutation in the editing domain of the alanyl-tRNA synthetase gene that compromises the proofreading activity of this enzyme during aminoacylation of tRNAs. These findings demonstrate that disruption of translational fidelity in terminally differentiated neurons leads to the accumulation of misfolded proteins and cell death, and provide a novel mechanism underlying neurodegeneration.
- Published
- 2006
19. Thenob2mouse, a null mutation inCacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses
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Akihiro Ikeda, Kirstan A. Vessey, Ronald E. Hurd, Britt A. Johnson, Neal S. Peachey, S. Nusinowitz, Catherine W. Morgans, Bo Chang, John R. Heckenlively, Nicholas C. Brecha, Ronald G. Gregg, Maureen A. McCall, Muriel T. Davisson, Philippa R. Bayley, Arlene A. Hirano, Dennis S. Rice, and Norm L. Hawes
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Retinal Ganglion Cells ,Calbindins ,Time Factors ,genetic structures ,Calcium Channels, L-Type ,Physiology ,Action Potentials ,Outer plexiform layer ,Dark Adaptation ,Biology ,Visual system ,Receptors, Metabotropic Glutamate ,Retinal ganglion ,Article ,Retina ,Mice ,Peanut Agglutinin ,S100 Calcium Binding Protein G ,Electroretinography ,Reaction Time ,medicine ,Animals ,Visual Pathways ,RNA, Messenger ,Outer nuclear layer ,Protein Kinase C ,Voltage-dependent calcium channel ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,Age Factors ,Dose-Response Relationship, Radiation ,Receptors, Neurokinin-3 ,Photoreceptor ribbon synapse ,Phosphoproteins ,Immunohistochemistry ,Mice, Mutant Strains ,Sensory Systems ,DNA-Binding Proteins ,Alcohol Oxidoreductases ,medicine.anatomical_structure ,Mutation ,Synapses ,Calcium Channels ,sense organs ,Co-Repressor Proteins ,Neuroscience ,Photic Stimulation - Abstract
Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, mutations in theCacna1fgene, encoding the α1Fsubunit of VDCCs, underlie the incomplete form of X-linked congenital stationary night blindness (CSNB2). These mutations impair synaptic transmission from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and functional characterizations of the retina in thenob2(no b-wave 2) mouse, a naturally occurring mutant caused by a null mutation inCacna1f. Not surprisingly, theb-waves of both the light- and dark-adapted electroretinogram are abnormal innob2mice. The outer plexiform layer (OPL) is disorganized, with extension of ectopic neurites through the outer nuclear layer that originate from rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells. These ectopic neurites continue to express mGluR6, which is frequently associated with profiles that label with the presynaptic marker Ribeye, indicating potential points of ectopic synapse formation. However, the morphology of the presynaptic Ribeye-positive profiles is abnormal. While cone pedicles are present their morphology also appears compromised. Characterizations of visual responses in retinal ganglion cellsin vivo, under photopic conditions, demonstrate that ON-center cells have a reduced dynamic range, although their basic center-surround organization is retained; no alteration in the responses of OFF-center cells was evident. These results indicate thatnob2mice are a valuable model in which to explore the pathophysiological mechanisms associated withCacna1fmutations causing CSNB2, and the subsequent effects on visual information processing. Further, thenob2mouse represents a model system in which to define the signals that guide synapse formation and/or maintenance in the OPL.
- Published
- 2006
20. Discovery Genetics - The History and Future of Spontaneous Mutation Research
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Laura G. Reinholdt, Muriel T. Davisson, David E. Bergstrom, and Leah Rae Donahue
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Genetics ,Mammalian Genetics ,Mutagenesis (molecular biology technique) ,Human genome ,General Medicine ,Biology ,Gene ,Genetic analysis ,Phenotype ,Forward genetics ,DNA sequencing ,Article - Abstract
Historically, spontaneous mutations in mice have served as valuable models of heritable human diseases, contributing substantially to our understanding of both disease mechanisms and basic biological pathways. While advances in molecular technologies have improved our ability to create mouse models of human disease through targeted mutagenesis and transgenesis, spontaneous mutations continue to provide valuable research tools for discovery of novel genes and functions. In addition, the genetic defects caused by spontaneous mutations are molecularly similar to mutations in the human genome and, therefore, often produce phenotypes that more closely resemble those characteristic of human disease than do genetically engineered mutations. Due to the rarity with which spontaneous mutations arise and the animal-intensive nature of their genetic analysis, large-scale spontaneous mutation analysis has traditionally been limited to large mammalian genetics institutes. More recently, ENU mutagenesis and new screening methods have increased the rate of mutant strain discovery, and high-throughput DNA sequencing has enabled rapid identification of the underlying genes and their causative mutations. Here we discuss the continued value of spontaneous mutations for biomedical research. Curr. Protoc. Mouse Biol. 2:103-118 © 2012 by John Wiley & Sons, Inc. Keywords: spontaneous mutations; mouse models; forward genetics; biomedical research
- Published
- 2014
21. Trak1 mutation disrupts GABAA receptor homeostasis in hypertonic mice
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Sandra L, Gilbert, Li, Zhang, Michele L, Forster, Jeffrey R, Anderson, Tamaki, Iwase, Betty, Soliven, Leah Rae, Donahue, Hope O, Sweet, Roderick T, Bronson, Muriel T, Davisson, Robert L, Wollmann, and Bruce T, Lahn
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medicine.medical_specialty ,Molecular Sequence Data ,Central nervous system ,Gene Expression ,Biology ,Mice ,Muscle Hypertonia ,Anterior Horn Cells ,Pons ,Internal medicine ,Genetics ,medicine ,Animals ,Homeostasis ,Humans ,RNA, Messenger ,Kinesin binding ,Muscle, Skeletal ,Receptor ,Inclusion Bodies ,Dystonia ,Diazepam ,Electromyography ,GABAA receptor ,Homozygote ,Motor neuron ,Physical Chromosome Mapping ,Receptors, GABA-A ,medicine.disease ,Chromosomes, Mammalian ,Adaptor Proteins, Vesicular Transport ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Mutation ,Hypertonia ,medicine.symptom ,Carrier Proteins - Abstract
Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.
- Published
- 2005
22. Mouse models of ocular diseases
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D. Howell, Steven Nusinowitz, Norm L. Hawes, Ronald E. Hurd, T H Roderick, J. Wang, John R. Heckenlively, Muriel T. Davisson, and Bo Chang
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Retinal degeneration ,Eye Diseases ,genetic structures ,Physiology ,Eye disease ,Glaucoma ,Biology ,Genetic analysis ,Cataract ,Chromosomes ,Ophthalmoscopy ,Mice ,Retinal Diseases ,Cataracts ,Gene mapping ,Electroretinography ,medicine ,Animals ,Eye Abnormalities ,Genetics ,medicine.diagnostic_test ,Anatomy ,medicine.disease ,Mice, Mutant Strains ,eye diseases ,Sensory Systems ,Disease Models, Animal ,sense organs - Abstract
The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to discover genetically determined eye variations and disorders. In this paper, we list and describe mouse models for ocular research available from Mouse Eye Mutant Resource at The Jackson Laboratory. While screening mouse strains and stocks at The Jackson Laboratory (TJL) for genetic mouse models of human ocular disorders, we have identified numerous spontaneous or naturally occurring mutants. We characterized these mutants using serial indirect ophthalmoscopy, fundus photography, electroretinography (ERG) and histology, and performed genetic analysis including linkage studies and gene identification. Utilizing ophthalmoscopy, electroretinography, and histology, to date we have discovered 109 new disorders affecting all aspects of the eye including the lid, cornea, iris, lens, and retina, resulting in corneal disorders, glaucoma, cataracts, and retinal degenerations. The number of known serious or disabling eye diseases in humans is large and affects millions of people each year. Yet research on these diseases frequently is limited by the obvious restrictions on studying pathophysiologic processes in the human eye. Likewise, many human ocular diseases are genetic in origin, but appropriate families often are not readily available for genetic studies. Mouse models of inherited ocular disease provide powerful tools for rapid genetic analysis, characterization, and gene identification. Because of the great similarity among mammalian genomes, these findings in mice have direct relevance to the homologous human conditions.
- Published
- 2005
23. Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome
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Noemí Rueda, Muriel T. Davisson, Cecilia Schmidt, Eva María del Pozo García, Carmen Martínez-Cué, and Jesús Flórez
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Male ,congenital, hereditary, and neonatal diseases and abnormalities ,animal diseases ,Morris water navigation task ,Physiology ,Trisomy ,Environment ,Motor Activity ,Developmental psychology ,Mice ,Mice, Neurologic Mutants ,Behavioral Neuroscience ,chemistry.chemical_compound ,Cognition ,Adrenocorticotropic Hormone ,Corticosterone ,mental disorders ,Reaction Time ,medicine ,Animals ,Weaning ,Testosterone ,Maze Learning ,Swimming ,Analysis of Variance ,Mice, Inbred C3H ,Environmental enrichment ,Behavior, Animal ,Aggression ,Disease Models, Animal ,Social Dominance ,chemistry ,Anxiety ,Analysis of variance ,Down Syndrome ,medicine.symptom ,Psychology - Abstract
Ts65Dn mouse is the most widely accepted model for Down syndrome. We previously showed that environmental enrichment improved spatial learning in female but deteriorated it in male Ts65Dn mice. This study analyzed the factors contributing to the disturbed cognition of male Ts65Dn mice after enriched housing, by allocating male control and Ts65Dn mice in four conditions after weaning: small (n = 2-3) and large group (n = 8-10) housing, and enriched housing in small (2-3) and large groups (8-10). Learning, aggressive behavior, anxiety-like behavior and biochemical correlates of stress were evaluated when Ts65Dn and control mice were 4-5 months old. Environmental enrichment in large mixed colonies of Ts65Dn and diploid littermates disturbed behavioral and learning skills of Ts65Dn mice in the Morris water maze. ACTH and testosterone levels were not modified in any group of mice. Ts65Dn and control mice subjected to enriched housing in large groups and Ts65Dn mice housed in large groups showed higher corticosterone levels. Aggressive behavior was evaluated by measuring the number of attacks performed in the presence of an intruder. Ts65Dn mice performed less attacks than controls in all conditions, especially after enriched housing, indicating subordination. In the plus maze, cognitive aspects (i.e. risk assessment) and motor components (open arm avoidance) of anxiety behavior were evaluated; no difference in any condition was found. It is suggested that an excess of social and/or physical stimulation in Ts65Dn mice may affect cognition by disturbing the emotional and behavioral components of the learning process.
- Published
- 2005
24. Mouse models of Down syndrome
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Muriel T. Davisson
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Drug Discovery ,Molecular Medicine - Published
- 2005
25. Discovery Genetics: Serendipity in Basic Research
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Muriel T. Davisson
- Subjects
Genetics ,Serendipity ,General Medicine ,Research opportunities ,Breeding ,Biology ,Mice, Mutant Strains ,General Biochemistry, Genetics and Molecular Biology ,Forward genetics ,Human genetics ,Disease Models, Animal ,Mice ,Human disease ,Research Design ,Basic research ,Animals, Laboratory ,Mutation ,Animals ,Animal Science and Zoology - Abstract
The role of serendipity in science has no better example than the discovery of spontaneous mutations that leads to new mouse models for research. The approach of finding phenotypes and then carrying out genetic analysis is called forward genetics. Serendipity is a key component of discovering and developing mice with spontaneous mutations into animal models of human disease. In this article, the role of serendipity in discovering and developing mouse models is described within a program at The Jackson Laboratory that capitalizes on serendipitous discoveries in large breeding colonies. Also described is how any scientists working with mice can take advantage of serendipitous discoveries as a research strategy to develop new models. Spontaneous mutations cannot be planned but happen in all research mouse colonies and are discovered as unexpected phenotypes. The alert scientist or technician can rationally exploit such chance observations to create new research opportunities.
- Published
- 2005
26. Report on the ‘Expert Workshop on the Biology of Chromosome 21: towards gene-phenotype correlations in Down syndrome’, held June 11–14, 2004, Washington D.C
- Author
-
Muriel T. Davisson, Yoram Groner, Melanie April Pritchard, L S Crnic, David Patterson, Katheleen Gardiner, William C. Mobley, and Stylianos E. Antonarakis
- Subjects
Down syndrome ,Biology ,Bioinformatics ,Mice ,Synaptic Vesicles/genetics/metabolism ,Reactive Oxygen Species/metabolism ,Mitochondria/genetics/pathology ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Gene ,Genetics (clinical) ,ddc:616 ,Leukemia/genetics ,Intracellular Signaling Peptides and Proteins ,Endocytosis/genetics ,Calcineurin/antagonists & inhibitors ,medicine.disease ,Phenotype ,Chromosomes, Human, Pair 21/ genetics ,Disease Models, Animal ,Genes ,Amyloid beta-Protein Precursor/genetics/metabolism ,Down Syndrome/complications/ genetics ,Signal Transduction/genetics ,Chromosome 21 ,Muscle Proteins/genetics/physiology - Published
- 2004
27. Building protein interaction maps for Down's syndrome
- Author
-
Linda S. Crnic, Muriel T. Davisson, and Katheleen Gardiner
- Subjects
TBX1 ,Genetics ,Candidate gene ,Alternative splicing ,Biology ,Biochemistry ,Gene dosage ,Protein–protein interaction ,Protein Interaction Mapping ,Animals ,Humans ,Down Syndrome ,RNA Processing, Post-Transcriptional ,Chromosome 21 ,Molecular Biology ,Gene ,Function (biology) ,Signal Transduction - Abstract
Now that the complete sequences for human chromosome 21 and the orthologous mouse genomic regions are known, reasonably complete, conserved, protein-coding gene catalogues are also available. The central issue now facing Down's syndrome researchers is the correlation of increased expression of specific, normal, chromosome 21 genes with the development of specific deficits in learning and memory. Because of the number of candidate genes involved, the number of alternative splice variants of individual genes and the number of pathways in which these genes function, a pathway analysis approach will be critical to success. Here, three examples, both gene specific and pathway related, that would benefit from pathway analysis are discussed: (1) the potential roles of eight chromosome 21 proteins in RNA processing pathways; (2) the chromosome 21 protein intersectin 1 and its domain composition, alternative splicing, protein interactions and functions; and (3) the interactions of ten chromosome 21 proteins with components of the mitogen-activated protein kinase and the calcineurin signalling pathways. A productive approach to developing gene-phenotype correlations in Down's syndrome will make use of known and predicted functions and interactions of chromosome 21 genes to predict pathways that may be perturbed by their increased levels of expression. Investigations may then be targeted in animal models to specific interactions, intermediate steps or end-points of such pathways and the downstream - perhaps amplified - consequences of gene dosage directly assessed. Once pathway perturbations have been identified, the potential for rational design of therapeutics becomes practical.
- Published
- 2004
28. Mouse models of Down syndrome: how useful can they be? Comparison of the gene content of human chromosome 21 with orthologous mouse genomic regions
- Author
-
Lawrence Bechtel, Katheleen Gardiner, Muriel T. Davisson, and Andrew Fortna
- Subjects
Male ,Transcription, Genetic ,Chromosomes, Human, Pair 21 ,Gene Expression ,Biology ,Synteny ,Mice ,Chromosome 16 ,Species Specificity ,Gene expression ,Genetics ,Homologous chromosome ,Animals ,Humans ,RNA, Antisense ,Gene ,Alternative splicing ,General Medicine ,Chromosomes, Mammalian ,Phenotype ,Mice, Inbred C57BL ,Alternative Splicing ,Disease Models, Animal ,Genes ,Female ,Down Syndrome ,Chromosome 21 - Abstract
With an incidence of approximately 1 in 700 live births, Down syndrome (DS) remains the most common genetic cause of mental retardation. The phenotype is assumed to be due to overexpression of some number of the >300 genes encoded by human chromosome 21. Mouse models, in particular the chromosome 16 segmental trisomies, Ts65Dn and Ts1Cje, are indispensable for DS-related studies of gene-phenotype correlations. Here we compare the updated gene content of the finished sequence of human chromosome 21 (364 genes and putative genes) with the gene content of the homologous mouse genomic regions (291 genes and putative genes) obtained from annotation of the public sector C57Bl/6 draft sequence. Annotated genes fall into one of three classes. First, there are 170 highly conserved, human/mouse orthologues. Second, there are 83 minimally conserved, possible orthologues. Included among the conserved and minimally conserved genes are 31 antisense transcripts. Third, there are species-specific genes: 111 spliced human transcripts show no orthologues in the syntenic mouse regions although 13 have homologous sequences elsewhere in the mouse genomic sequence, and 38 spliced mouse transcripts show no identifiable human orthologues. While these species-specific genes are largely based solely on spliced EST data, a majority can be verified in RNA expression experiments. In addition, preliminary data suggest that many human-specific transcripts may represent a novel class of primate-specific genes. Lastly, updated functional annotation of orthologous genes indicates genes encoding components of several cellular pathways are dispersed throughout the orthologous mouse chromosomal regions and are not completely represented in the Down syndrome segmental mouse models. Together, these data point out the potential for existing mouse models to produce extraneous phenotypes and to fail to produce DS-relevant phenotypes.
- Published
- 2003
29. Annotation of Human Chromosome 21 for Relevance to Down Syndrome: Gene Structure and Expression Analysis
- Author
-
Katheleen Gardiner, D. Slavov, Lawrence Bechtel, and Muriel T. Davisson
- Subjects
Genetics ,TBX1 ,Chromosomes, Human, Pair 21 ,Gene Expression Profiling ,Alternative splicing ,Biology ,Gene expression profiling ,Mice ,Complete sequence ,Gene mapping ,Animals ,Humans ,Human genome ,Down Syndrome ,Chromosome 21 ,Gene - Abstract
Down syndrome is caused by an extra copy of human chromosome 21 and the resultant dosage-related overexpression of genes contained within it. To efficiently direct experiments to determine specific gene-phenotype correlations, it is necessary to identify all genes within 21q and assess their functional associations and expression patterns. Analysis of the complete finished sequence of 21q resulted in annotated 225 genes and gene models, most of which were incomplete and/or had little or no experimental verification. Here we correct or complete the genomic structures of 16 genes, 4 of which were not reported in the annotation of the complete sequence. Our data include the identification of six genes encoding short or ambiguous open reading frames; the identification of three cases in which alternative splicing produces two structurally unrelated protein sequences; and the identification of six genes encoding proteins with functional motifs, two genes with unusually low similarity to their orthologous mouse proteins, and four genes with significant conservation in Drosophila melanogaster. We further demonstrate that an additional nine gene models represent bona fide transcripts and develop expression patterns for these genes plus nine additional novel chromosome 21 genes and four paralogous genes mapping elsewhere in the human genome. These data have implications for generating complete transcript maps of chromosome 21 and for the entire human genome, and for defining expression abnormalities in Down syndrome and mouse models.
- Published
- 2002
30. A Gja8 (Cx50) point mutation causes an alteration of alpha3 connexin (Cx46) in semi-dominant cataracts of Lop10 mice
- Author
-
Norman L. Hawes, Woo-Kuen Lo, Xiaohua Gong, Muriel T. Davisson, Ryan Ojakian, Bo Chang, and Xin Wang
- Subjects
Genetic Markers ,Male ,Genotype ,Genetic Linkage ,Mutant ,Connexin ,Alpha (ethology) ,Biology ,Arginine ,medicine.disease_cause ,Cataract ,Connexins ,Mice ,Mice, Inbred AKR ,Lens, Crystalline ,Genetics ,medicine ,Animals ,Microphthalmos ,Point Mutation ,Missense mutation ,Codon ,Eye Proteins ,Molecular Biology ,Gene ,Crosses, Genetic ,Genetics (clinical) ,Genes, Dominant ,Mice, Inbred BALB C ,Mutation ,Base Sequence ,Point mutation ,Chromosome Mapping ,Sequence Analysis, DNA ,General Medicine ,Phenotype ,Molecular biology ,Pedigree ,Amino Acid Substitution ,Female ,sense organs - Abstract
Mutations of connexin alpha 8 (GJA8 or Cx50) and connexin alpha 3 (GJA3 or Cx46) in humans have been reported to cause cataracts with semi-dominant inheritance patterns. Targeted null mutations in Gja8 and Gja3 in mice cause cataracts with recessive inheritance. The molecular bases for these differences in inheritance patterns and the mechanism for cataractogenesis in these mutants are poorly understood. We recently mapped an autosomal semi-dominant cataract [lens opacity 10 (Lop10)] mutation to mouse chromosome 3 and identified a missense mutation (G-->C) in the Gja8 gene, which causes glycine at codon 22 to be replaced with arginine (G22R). Moreover, we demonstrated that the alpha 8 G22R isoform is a loss-of-function mutant for alpha 8, as well as a dominant mutation for reducing the phosphorylated forms of alpha 3 connexin in vivo. To test the hypothesis that the alteration of endogenous alpha 3 connexin in Lop10 mice led to a unique lens phenotype, we generated double mutant offspring between Lop10 and the Gja3(tm1) (alpha 3(-/-)) mice. The double homozygous mutant mice (Lop10/Lop10 alpha 3(-/-)) showed relatively normal lens cortical fibers compared to the Lop10 mice. A functional impairment of endogenous alpha 3 connexin is therefore partly responsible for cellular phenotypes in the Lop10 mice. This study has provided some novel molecular insights into mouse and human cataractogenesis caused by alpha 8 and alpha 3 mutations. These mouse models will be useful for investigating the mechanistic relationship between gap junction impairment and cataract formation.
- Published
- 2002
31. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis
- Author
-
Heather Fairfield, Polyxeni Gudis, Caleb Heffner, Ellen C. Akeson, Don Liu, Susan A. Cook, Stephen A. Murray, and Muriel T. Davisson
- Subjects
medicine.medical_specialty ,Physiology ,Organogenesis ,Kidney development ,Hydronephrosis ,Biology ,Kidney ,Internal medicine ,medicine ,Animals ,Chromosome 12 ,Breakpoint ,Gene Expression Regulation, Developmental ,medicine.disease ,Hypoplasia ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,Agenesis ,Urogenital Abnormalities ,Mutation (genetic algorithm) ,Mutation ,Cancer research ,Call for Papers ,Transcription Factors - Abstract
Many genes, including odd-skipped related 1 ( Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis.
- Published
- 2014
32. Mutations in the Human Orthologue of the Mouse underwhite Gene (uw) Underlie a New Form of Oculocutaneous Albinism, OCA4
- Author
-
J. M. Newton, John M. Gardner, Orit Cohen-Barak, Nobuko Hagiwara, Muriel T. Davisson, Richard A. King, and Murray H. Brilliant
- Subjects
Adult ,Male ,SLC45A2 ,Protein Conformation ,DNA Mutational Analysis ,Molecular Sequence Data ,SLC24A5 ,Eye ,medicine.disease_cause ,Mice ,Oculocutaneous albinism type 4 ,Antigens, Neoplasm ,Genetics ,medicine ,Animals ,Humans ,Genetics(clinical) ,Amino Acid Sequence ,RNA, Messenger ,TYRP1 ,Cloning, Molecular ,Alleles ,Conserved Sequence ,Genetics (clinical) ,OCA2 ,Mutation ,Symporters ,biology ,Pigmentation ,Homozygote ,Membrane Proteins ,Membrane Transport Proteins ,Proteins ,Articles ,Exons ,Physical Chromosome Mapping ,medicine.disease ,Oculocutaneous albinism ,eye diseases ,Albinism, Oculocutaneous ,Child, Preschool ,biology.protein ,Albinism ,Chromosomes, Human, Pair 5 ,Sequence Alignment - Abstract
Oculocutaneous albinism (OCA) affects approximately 1/20,000 people worldwide. All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation during eye development results in misrouting of the optic nerves, nystagmus, alternating strabismus, and reduced visual acuity. Loss of pigmentation in the skin leads to an increased risk for skin cancer. Two common forms and one infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with mutations of the P gene and accounts for approximately 50% of OCA worldwide. OCA3 (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1). Analysis of the TYR and P genes in patients with OCA suggests that other genes may be associated with OCA. We have identified the mouse underwhite gene (uw) and its human orthologue, which underlies a new form of human OCA, termed "OCA4." The encoded protein, MATP (for "membrane-associated transporter protein") is predicted to span the membrane 12 times and likely functions as a transporter.
- Published
- 2001
33. Availability and characterization of transgenic and knockout mice with behavioral manifestations: where to look and what to search for
- Author
-
Janan T. Eppig, John J. Sharp, Larry E. Mobraaten, Muriel T. Davisson, and Anna V. Anagnostopoulos
- Subjects
Mice, Knockout ,Genetics ,Internet ,Behavior, Animal ,Transgene ,Brain ,Gene targeting ,Mice, Transgenic ,Biology ,Mice ,Behavioral Neuroscience ,Phenotype ,Genetic typing ,Research community ,Databases, Genetic ,Knockout mouse ,Catalogs as Topic ,Animals ,Merge (version control) ,Gene knockout ,Web site - Abstract
Mice altered by transgenesis or gene targeting ("knockouts") have increasingly been employed as alternative effective tools in elucidating the genetic basis of neurophysiology and behavior. Standardization of specific behavioral paradigms and phenotyping strategies will ensure that these behavioral mouse mutants offer robust models for evaluating the efficacy of novel therapeutics in the treatment of hereditary neurological disorders. The Induced Mutant Resource (IMR) at The Jackson Laboratory (Bar Harbor, Maine, USA) imports, cryopreserves, develops, maintains, and distributes to the research community biomedically valuable stocks of transgenic and targeted mutant mice. Information on behavioral and neurological strains-including a phenotypic synopsis, husbandry requirements, strain availability, and genetic typing protocols-is available through the IMR database (http://www.jax.org/resources/documents/imr/). A current catalog of available strains is readily accessible via the JAX Mice Web site at http://jaxmice.jax.org/index.shtml. In addition, The Jackson Laboratory is now home to TBASE (http://tbase.jax.org/), a comprehensive, community database whose primary focus is on mouse knockouts. TBASE accommodates an exhaustive bibliographical resource for transgenic and knockout mice and provides a detailed phenotypic characterization of numerous behavioral knockouts that is primarily extracted from the literature. Concerted efforts to merge the two resources into a new, schematically reformed database are underway.
- Published
- 2001
34. Transgenic and knockout databases
- Author
-
Anna V. Anagnostopoulos, Muriel T. Davisson, Larry E. Mobraaten, and John J. Sharp
- Subjects
Genetics ,Database ,Transgene ,Genetic enhancement ,Mutant ,Gene targeting ,Experimental and Cognitive Psychology ,Biology ,computer.software_genre ,Phenotype ,Behavioral Neuroscience ,Targeted Mutation ,Hereditary Diseases ,computer ,Gene knockout - Abstract
Genetically engineered strains of mice, modified by transgenesis or gene targeting (“knockouts”) are being generated at an impressive rate and used, among other areas, as premiere research tools in deciphering the genetic basis of behavior. As behavioral phenotyping strategies continue to evolve, characterization of these “designer” mice will provide models to evaluate the efficacy of new pharmacological and gene therapy treatments in human hereditary diseases. Reported behavioral profiles include aberrant social, reproductive, and parental behaviors, learning and memory deficits, feeding disorders, aggression, anxiety-related behaviors, pain/analgesia, and altered responses to antidepressants, antipsychotics, ethanol, and psychostimulant drugs of abuse. The Induced Mutant Resource (IMR) at The Jackson Laboratory (TJL, Bar Harbor, ME, USA) imports, cryopreserves, develops, maintains, and distributes biomedically important stocks of transgenic and targeted mutant mice to the research community. Information on neurological/behavioral strains — including behavioral performance, husbandry requirements, strain availability, and genetic typing protocols — is provided through the IMR database ( http://www.jax.org/resources/documents/imr/ ). A catalog of available strains is readily accessible via the JAX® Mice website at http://jaxmice.jax.org/index.shtml . In addition, TJL is now host to TBASE ( http://tbase.jax.org/ ), a comprehensive, public-domain database with primary emphasis on mouse knockouts. TBASE contains an exhaustive list of knockout-related citations and provides an extensive phenotypic characterization of numerous behavioral mutants that is extracted directly from the literature. Present efforts to merge the two resources into a novel, schematically enhanced database, provisionally named Transgenic and Targeted Mutation Database (TTMD), will be briefly discussed.
- Published
- 2001
35. Mouse paracentric inversion In(3)55Rk mutates the urate oxidase gene
- Author
-
Christopher J. Calvano, James Mandell, Susan A. Cook, Norman L. Hawes, Kenneth R. Johnson, Thomas H. Roderick, Muriel T. Davisson, Roderick T. Bronson, and Ellen C. Akeson
- Subjects
Male ,Urate Oxidase ,DNA Mutational Analysis ,Biology ,Mice ,Gene mapping ,Genetics ,Animals ,RNA, Messenger ,Allele ,Molecular Biology ,Alleles ,Crosses, Genetic ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,Chromosomal inversion ,Breakpoint ,Chromosome Mapping ,Urate oxidase ,Karyotype ,Exons ,Null allele ,Molecular biology ,Mice, Mutant Strains ,Chromosome Banding ,Uric Acid ,Blotting, Southern ,Chromosome 3 ,Chromosome Inversion ,Mutation ,Female ,Kidney Diseases ,Polymorphism, Restriction Fragment Length - Abstract
The paracentric inversion In(3)55Rk on mouse Chromosome 3 (Chr 3) was induced by cesium irradiation. Genetic crosses indicate the proximal breakpoint cosegregates with D3Mit324 and D3Mit92; the distal breakpoint cosegregates with D3Mit127, D3Mit160, and D3Mit200. Giemsa-banded chromosomes show the inversion spans ∼80% of Chr 3. The proximal breakpoint occurs within band 3A2, not 3B as reported previously; the distal breakpoint occurs within band 3H3. Mice homozygous for the inversion exhibit nephropathy indicative of uricase deficiency. Southern blot analyses of urate oxidase, Uox, show two RFLPs of genomic mutant DNA: an EcoRI site between exons 4–8 and a BamHI site 3′ to exon 6. Mutant cDNA fails to amplify downstream of base 844 at the 3′ end of exon 7. FISH analysis of chromosomes from inversion heterozygotes, using a cosmid clone containing genomic wild-type DNA for Uox exons 2–4, shows that a 5′ segment of the mutated Uox allele on the inverted chromosome has been transposed from the distal breakpoint region to the proximal breakpoint region. Clinical, histopathological, and Northern analyses indicate that our radiation-induced mutation, uoxIn, is a putative null.
- Published
- 2001
36. A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse
- Author
-
A. Rapoport, Steven Nusinowitz, Natik I. Piriev, Muriel T. Davisson, John R. Heckenlively, Christine A. Kozak, Patsy M. Nishina, Norman L. Hawes, Debora B. Farber, Bo Chang, Michael Danciger, Thomas H. Roderick, and N. B. Akhmedov
- Subjects
Genetic Markers ,Retinal degeneration ,Retinal Disorder ,Molecular Sequence Data ,Receptors, Cytoplasmic and Nuclear ,Mice, Inbred Strains ,Biology ,Frameshift mutation ,Mice ,chemistry.chemical_compound ,Electroretinography ,medicine ,Animals ,Humans ,Coding region ,Amino Acid Sequence ,RNA, Messenger ,DNA Primers ,Sequence Deletion ,Messenger RNA ,Multidisciplinary ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Retinal Degeneration ,Chromosome Mapping ,Retinal ,Biological Sciences ,Orphan Nuclear Receptors ,medicine.disease ,Molecular biology ,Mice, Mutant Strains ,Mice, Inbred C57BL ,chemistry ,Suppression subtractive hybridization ,Codon, Terminator ,Retinal dysplasia ,Photoreceptor Cells, Vertebrate ,Transcription Factors - Abstract
The rd7 mouse, an animal model for hereditary retinal degeneration, has some characteristics similar to human flecked retinal disorders. Here we report the identification of a deletion in a photoreceptor-specific nuclear receptor (mPNR) mRNA that is responsible for hereditary retinal dysplasia and degeneration in the rd7 mouse. mPNR was isolated from a pool of photoreceptor-specific cDNAs originally created by subtractive hybridization of mRNAs from normal and photoreceptorless rd mouse retinas. Localization of the gene corresponding to mPNR to mouse Chr 9 near the rd7 locus made it a candidate for the site of the rd7 mutation. Northern analysis of total RNA isolated from rd7 mouse retinas revealed no detectable signal after hybridization with the mPNR cDNA probe. However, with reverse transcription–PCR, we were able to amplify different fragments of mPNR from rd7 retinal RNA and to sequence them directly. We found a 380-nt deletion in the coding region of the rd7 mPNR message that creates a frame shift and produces a premature stop codon. This deletion accounts for more than 32% of the normal protein and eliminates a portion of the DNA-binding domain. In addition, it may result in the rapid degradation of the rd7 mPNR message by the nonsense-mediated decay pathway, preventing the synthesis of the corresponding protein. Our findings demonstrate that mPNR expression is critical for the normal development and function of the photoreceptor cells.
- Published
- 2000
37. The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization
- Author
-
Norman L. Hawes, Simon W. M. John, Bo Chang, Richard S. Smith, Adriana Zabeleta, and Muriel T. Davisson
- Subjects
Aging ,Pathology ,medicine.medical_specialty ,genetic structures ,Locus (genetics) ,Retinal Neovascularization ,Biology ,Eye ,Mice ,Chromosome 16 ,Age related ,medicine ,Animals ,Fluorescein Angiography ,Retina ,Multidisciplinary ,Subretinal neovascularization ,medicine.diagnostic_test ,Chromosome Mapping ,Anatomy ,Biological Sciences ,Macular degeneration ,Fluorescein angiography ,medicine.disease ,eye diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,sense organs ,Choroid - Abstract
Ocular neovascularization is the leading cause of blindness in developed countries and often causes rapid loss of vision in age-related macular degeneration. Acute visual loss is most often due to hemorrhage from new vessels that have extended from the choroid into the subretinal space. Growth of abnormal vessels beneath the retina in this condition is known as subretinal neovascularization (SRN). Age-related animal models of macular degeneration and SRN have not been described. Current animal models of SRN depend on chemical or physical stimuli to initiate growth of subretinal vessels. The genes responsible for age-related human macular degeneration with SRN have not been firmly identified. We report an angiogenic phenotype in Bst / + mice that is age-related, clinically evident, and resembles human SRN. This represents a spontaneous, genetically determined model of SRN. Bst / + mice offer the possibility of exploring the molecular mechanisms of SRN without the need for exogenous agents.
- Published
- 2000
38. Lop12, a Mutation in Mouse Crygd Causing Lens Opacity Similar to Human Coppock Cataract
- Author
-
Xin Wang, John R. Heckenlively, Richard S. Smith, Norman L. Hawes, Muriel T. Davisson, Bo Chang, Ellen C. Akeson, Xiaohua Gong, and Thomas H. Roderick
- Subjects
Male ,Protein Folding ,Candidate gene ,DNA, Complementary ,Genetic Linkage ,DNA Mutational Analysis ,Biology ,Cataract ,Homology (biology) ,Gene product ,Mice ,Exon ,Species Specificity ,Gene mapping ,Gene cluster ,Genetics ,Animals ,Humans ,Crosses, Genetic ,Terminator Regions, Genetic ,Mice, Inbred BALB C ,Chromosome Mapping ,Crystallins ,eye diseases ,Stop codon ,Disease Models, Animal ,Female ,Protein folding - Abstract
A new cataract mutation was discovered in an ongoing program to identify new mouse models of hereditary eye disease. Lens opacity 12 (Lop12) is a semidominant mutation that results in an irregular nuclear lens opacity similar to the human Coppock cataract. Lop12 is associated with a small nonrecombining segment that maps to mouse Chromosome 1 close to the eye lens obsolescence mutation (Cryge(Cat2-Elo)), a member of the gamma-crystallin gene cluster (Cryg). Using a systemic candidate gene approach to analyze the entire Cryg cluster, a G to A transition was found in exon 3 of Crygd associated with the Lop12 mutation and has been designated Crygd(Lop12). The mutation Crygd(Lop12) leads to the formation of an in-frame stop codon that produces a truncated protein of 156 amino acids. It is predicted that the defective gene product alters protein folding of the gamma-crystallin(s) and results in lens opacity.
- Published
- 2000
39. Lens epithelial proliferation cataract in segmental trisomy involving mouse Chromosomes 4 and 17
- Author
-
Belinda S. Harris, Muriel T. Davisson, Richard S. Smith, Kenneth R. Johnson, John P. Sundberg, and Norman L. Hawes
- Subjects
Male ,Genetically modified mouse ,Anterior subcapsular cataract ,Translocation Breakpoint ,Chromosome Disorders ,Trisomy ,Chromosomal translocation ,Biology ,medicine.disease_cause ,Cataract ,Chromosomes ,Mice ,Cataracts ,Lens, Crystalline ,Genetics ,medicine ,Animals ,Chromosome Aberrations ,Mice, Inbred C3H ,Mutation ,Epithelial Cells ,DNA ,Blotting, Northern ,medicine.disease ,Phenotype ,Molecular biology ,Mice, Inbred C57BL ,Blotting, Southern ,Animals, Newborn ,Mice, Inbred DBA ,Female ,sense organs ,Cell Division - Abstract
A dominant induced mutation in the mouse, tightly associated with a reciprocal chromosomal translocation between Chrs 4 and 17, causes abnormal head tossing and circling behavior (the translocation induced circling mutation, Tim). Affected mice develop an unusual anterior subcapsular cataract that appears after birth and is progressive. The most likely explanation for the phenotypic observations is that the translocation breakpoint disrupted a gene or its regulation. Although the Mos protooncogene is located close to the translocation breakpoint and transgenic mice that overexpress Mos demonstrate cataracts and circling behavior, there were no gross changes in the Mos gene or in its level of expression. The morphological changes observed in the lens resemble those seen in some human congenital cataract syndromes.
- Published
- 1999
40. The Mouse Genome Database (MGD): genetic and genomic information about the laboratory mouse
- Author
-
Joel E. Richardson, Janan T. Eppig, Judith A. Blake, and Muriel T. Davisson
- Subjects
Genetics ,Genetic marker ,Representative sequences ,Laboratory mouse ,Gene family ,Biology ,Gene ,Genome ,Phenotype ,Homology (biology) - Abstract
The Mouse Genome Database (MGD) focuses on the integration of mapping, homology, polymorphism and molecular data about the laboratory mouse. Detailed descriptions of genes including their chromosomal location, gene function, disease associations, mutant phenotypes, molecular polymorphisms and links to representative sequences including ESTs are integrated within MGD. The association of information from experiment to gene to genome requires careful coordination and implementation of standardized vocabularies, unique nomenclature constructions, and detailed information derived from multiple sources. This information is linked to other public databases that focus on additional information such as expression patterns, sequences, bibliographic details and large mapping panel data. Scientists participate in the curation of MGD data by generating the Chromosome Committee Reports, consulting on gene family nomenclature revisions, and providing descriptions of mouse strain characteristics and of new mutant phenotypes. MGD is accessible at http://www.informatics.jax.org
- Published
- 1999
41. Ts65Dn: un modèle murin du syndrome de Down
- Author
-
Muriel T. Davisson and Alberto C.S. Costa
- Subjects
Gynecology ,medicine.medical_specialty ,Animal model ,medicine ,General Medicine ,Biology ,Trisomy ,medicine.disease ,Microbiology - Abstract
Le syndrome de Down (SD), affection complexe causee par la trisomie du chromosome 21, est un probleme de sante important en raison de la multitude des effets congenitaux associes et des troubles postnatals. Les mecanismes cellulaires qui sous-tendent les caracteristiques neurologiques ou non du SD sont encore mal connus, et des progres ne pourront etre realises qu'avec l'aide de modeles murins genetiquement definis avec precision.
- Published
- 1998
42. Brief communication. Juvenile bare: a new hair loss mutation on chromosome 7 of the mouse
- Author
-
Priscilla W. Lane, Muriel T. Davisson, Susan A. Cook, Patricia F Ward-Bailey, L. R. Donahue, and Roderick T. Bronson
- Subjects
Chromosome 7 (human) ,Mutation ,integumentary system ,Mutant ,Biology ,medicine.disease_cause ,Hair follicle ,medicine.disease ,Molecular biology ,Follicle ,medicine.anatomical_structure ,Hair loss ,Genetics ,medicine ,Juvenile ,Molecular Biology ,Genetics (clinical) ,X-linked recessive inheritance ,Biotechnology - Abstract
We describe a new juvenile hair loss mutant in the mouse in which the hair follicle follows irregular pathways to the surface and generally becomes dystrophic when the mouse is about 23 days of age. Skin from mutant mice older than 1 month of age is histologically normal, although adult mutant mice show a slightly more sparse coat than normal. Grafts of mutant littermates skin to SCID hosts indicate that the condition is probably a systemic response rather than one of the follicle per se. The hair loss is caused by a recessive mutation, which we have named juvenile bare (jb), located on proximal chromosome 7.
- Published
- 1998
43. The Mouse Gene Map
- Author
-
Stephen Rockwood, Muriel T. Davisson, Jennifer J. Merriam, Janan T. Eppig, and Dirck W. Bradt
- Subjects
Text mining ,Gene map ,business.industry ,MEDLINE ,Animal Science and Zoology ,General Medicine ,Computational biology ,Biology ,business ,General Biochemistry, Genetics and Molecular Biology - Published
- 1998
44. Strategies for managing an ever increasing mutant mouse repository
- Author
-
Robert Taft and Muriel T. Davisson
- Subjects
Genetics ,Mutation ,Genetically engineered ,General Neuroscience ,Strain (biology) ,Transgene ,Quantitative Trait Loci ,Mutant ,Mice, Inbred Strains ,Mice, Transgenic ,Biology ,Quantitative trait locus ,medicine.disease_cause ,Mice, Mutant Strains ,Mice ,Inbred strain ,medicine ,Animals ,Neurology (clinical) ,Molecular Biology ,Gene ,Developmental Biology - Abstract
Over 10,000 mouse strains and more than 20,000 mouse ES cells containing gene-trapped or targeted mutations are available to researchers. The mouse strains and stocks include those with spontaneous, genetically engineered and induced mutations, as well as 100s of inbred strains and strain panels, valuable for quantitative trait locus (QTL) and modifier gene identification. Current worldwide initiatives are expected to result in multiple mutations in every mouse gene in the first 10 years of the 21st century. Managing the rapid and cost effective distribution of these burgeoning resources to scientists around the world will be challenging for scientists and mouse repositories. Here we describe new strategies for managing and distributing mice.
- Published
- 2006
45. Birthdate and Cell Marker Analysis of Scrambler: A Novel Mutation Affecting Cortical Development with a Reeler-Like Phenotype
- Author
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Muriel T. Davisson, Jorge L. González, Dan Goldowitz, Hope O. Sweet, Christopher J. Russo, and Christopher A. Walsh
- Subjects
Cell Adhesion Molecules, Neuronal ,Mutant ,Hippocampus ,Gestational Age ,Nerve Tissue Proteins ,medicine.disease_cause ,Cerebellar Cortex ,Genetic Heterogeneity ,Mice ,Mice, Neurologic Mutants ,Reeler ,Cell Movement ,Cortex (anatomy) ,Morphogenesis ,medicine ,Animals ,Cell Lineage ,Reelin ,Cerebral Cortex ,Neurons ,Extracellular Matrix Proteins ,Mutation ,biology ,General Neuroscience ,Serine Endopeptidases ,Neurogenesis ,Gene Expression Regulation, Developmental ,Articles ,DAB1 ,Cell biology ,Reelin Protein ,Phenotype ,medicine.anatomical_structure ,nervous system ,biology.protein ,Neuroscience ,Biomarkers - Abstract
The reeler mutation in mice produces an especially well characterized disorder, with systematically abnormal migration of cerebral cortical neurons. The reeler gene encodes a large protein, termed Reelin, that in the cortex is synthesized and secreted exclusively in the Cajal-Retzius neurons of the cortical marginal zone (D’Arcangelo et al., 1995). In reeler mutant mice, loss of Reelin protein is associated with a systematic loss of the normal, “inside-out” sequence of neurogenesis in the cortex: neurons are formed in the normal sequence but become localized in the cortex in a somewhat inverted, although relatively disorganized “outside-in” pattern. Here we show that the scrambler mutant mouse exhibits a loss of lamination in the cortex and hippocampus that is indistinguishable from that seen in the reeler mouse. We use BrdU birthdating studies to show that scrambler cortex shows a somewhat inverted “outside-in” sequence of birthdates for cortical neurons that is similar to that previously described in reeler cortex. Finally, we perform staining with the CR-50 monoclonal antibody (Ogawa et al., 1995), which recognizes the Reelin protein (D’Arcangelo et al., 1997). We show that Reelin immunoreactivity is present in the scrambler cortex in a normal pattern, suggesting that Reelin is synthesized and released normally. Our data suggest that scrambler is a mutation in the same gene pathway as the reeler gene (Relnrl) and is most likely downstream ofRelnrl.
- Published
- 1997
46. NOMENCLATURE
- Author
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Janan T. Eppig, Muriel T. Davisson, Lois J. Maltais, and Judith A. Blake
- Subjects
Genetics ,Gene nomenclature ,Pseudogene ,Biology ,Computer communication networks ,Nomenclature ,Gene ,Genome ,Mice transgenic - Published
- 1997
47. MEETING REPORT
- Author
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Lois J. Maltais, Susan Povey, James E. Womack, Muriel T. Davisson, JA White, Janan T. Eppig, and Judith A. Blake
- Subjects
Genetics ,Biological data ,Biological database ,Unique gene ,Biology ,World Wide Web ,Gene nomenclature ,ComputingMethodologies_PATTERNRECOGNITION ,Controlled vocabulary ,ComputingMethodologies_GENERAL ,Mammalian genome ,Nomenclature ,Information explosion - Abstract
Scientists, whether species gene mappers or biological database developers, are looking for consistency and stability in the naming of genomic segments. For mammalian genome groups, this means relaxing the insistence on constant name revisions, allowing the functional and location information to be encoded elsewhere in the databases through the development of improved classification systems and controlled vocabularies. For gene discoverers, it means cooperation to determine unique gene designations without imposing too much knowledge in the naming process. For both groups, the power of database connections and structures needs to be exploited further to facilitate use of the massive amount of biological data being encoded. This workshop allowed the voices of many active participants in the naming and mapping of genes to be heard. The discussions reflected the intense interest in the stabilization of gene names despite the rapid advances in our knowledge of gene function and evolutionary relationships. Relaxation of the constraints and conventions on the gene naming effort that required the encapsulation of gene function or other attributes in the symbol will promote stability in the naming efforts. The development of multiple classifications and more robust data-base structures to support the information explosion releases the gene names from constantly changing to reflect our current knowledge. The gain in stability of gene nomenclature will be a welcome result.
- Published
- 1997
48. Genetic and Physical Maps of the Stargazer Locus on Mouse Chromosome 15
- Author
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Verity A. Letts, Wayne N. Frankel, Jessica P. Kirley, Hope O. Sweet, Muriel T. Davisson, and A Valenzuela
- Subjects
Genetic Markers ,Male ,Candidate gene ,Mice, Inbred A ,Locus (genetics) ,Mice ,Mice, Neurologic Mutants ,Chromosome 15 ,Species Specificity ,Gene mapping ,Genetics ,Animals ,Humans ,Cloning, Molecular ,Chromosomes, Artificial, Yeast ,Gene ,Crosses, Genetic ,DNA Primers ,Mice, Inbred C3H ,Base Sequence ,Contig ,biology ,Chromosome Mapping ,biology.organism_classification ,Mice, Inbred C57BL ,Disease Models, Animal ,Epilepsy, Absence ,Genetic marker ,Mutation ,Female ,Stargazer ,Microsatellite Repeats - Abstract
The stargazer mouse mutation causes absence seizures that are more prolonged and frequent than any other petit mal mouse model. Stargazer mice also have an ataxic gait and vestibular problems, including a distinctive head-tossing motion. From the genotyping of a large intersubspecific cross, a panel of 53 recombinant DNAs between D15Mit29 and D15Mit2 has been assembled, and a fine genetic map of the stargazer region has been constructed on mouse Chromosome 15. The stargazer locus has been mapped between D15Mit30 and the parvalbumin gene, and six candidate genes have been excluded by genetic linkage analysis. A physical contig of YACs, BACs, and P1s stretching 1.1 Mb from D15Mit30 to the somatostatin receptor 3 gene is reported, and the DNA interval including the stargazer locus has been narrowed to 150 kb.
- Published
- 1997
49. Forebrain overgrowth (fog): A new mutation in the mouse affecting neural tube development
- Author
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Susan A. Cook, Roderick T. Bronson, Sebastian Ullrich, Belinda S. Harris, Thomas Franz, and Muriel T. Davisson
- Subjects
Genetics ,Embryology ,genetic structures ,Neural tube defect ,Cerebrum ,Health, Toxicology and Mutagenesis ,Mesenchyme ,Mutant ,Neural tube ,Biology ,Toxicology ,medicine.disease ,Cell biology ,Encephalocele ,medicine.anatomical_structure ,Forebrain ,Mutation (genetic algorithm) ,medicine ,Developmental Biology - Abstract
Forebrain overgrowth, fog, is a spontaneous autosomal recessive mutation in the mouse producing forebrain, lumbo-sacral, and facial defects. The defects appear to result from excessive growth or cellular proliferation leading to abnormalities in neural tube closure. Three unique features of the mutant are: (1) the growth of telencephalon cells into the surrounding mesenchyme, (2) presence of an encephalocele through the midline cleft in some mutants, and (3) dissociation of the tail defect from the caudal neural tube defect. We used an intersubspecific intercross between mice carrying the fog mutation and mice from an inbred Mus musculus castaneus strain (CAST/Ei) to map the fog mutation to mouse Chromosome 10 near D10Mit262 and D10Mit230 in a region with several potential candidate genes.
- Published
- 1997
50. Cerebellar deficient folia (cdf): A new mutation on mouse Chromosome 6
- Author
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L. R. Donahue, Roderick T. Bronson, Susan A. Cook, Muriel T. Davisson, and Nissim Ben-Arie
- Subjects
Male ,Cerebellum ,Genetic Linkage ,Lurcher ,Genes, Recessive ,Biology ,medicine.disease_cause ,Chromosomes ,Cerebellar Cortex ,Mice ,Genetic linkage ,Genetics ,medicine ,Animals ,Gene ,Mice, Inbred C3H ,Mutation ,Chromosome Mapping ,Chromosome ,Phenotype ,Molecular biology ,Mice, Mutant Strains ,medicine.anatomical_structure ,Cerebellar cortex ,Female - Abstract
Cerebellar deficient folia, cdf, is a spontaneous autosomal recessive mutation in the mouse with unique pathology; the cerebellar cortex of the cdf/cdf mouse has only 7 folia instead of 10, which is the normal count for the C3H/HeJ strain in which this mutation arose. The cerebellum of the cdf/cdf mouse is hypoplastic and contains mineral deposits in the ventral vermis that are not present in controls. We used an intersubspecific intercross between C3H/HeSnJ-cdf/+ and Mus musculus castaneus (CAST/Ei) to map the cdf mutation to Chromosome (Chr) 6. The most likely gene order is D6Mit16- (cdf D6Mit3)- D6Mit70- D6Mit29- D6Mit32, which positions cdf distal to lurcher (Lc) and proximal to motor neuron degeneration 2 (mnd2). The definitive visible phenotypes and histopathologies of cdf Lc, and mnd.2 support our mapping evidence that cdf is a distinct gene. The novel pathology of cdf should help elucidate the complicated process of cerebellar folia patterning and development. cdf recombined with mouse atonal homolog 1, Math1, the mouse homolog of the Drosophila atonal gene.
- Published
- 1997
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