12 results on '"John Seavitt"'
Search Results
2. The occurrence of tarsal injuries in male mice of C57BL/6N substrains in multiple international mouse facilities.
- Author
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Eleanor Herbert, Michelle Stewart, Marie Hutchison, Ann M Flenniken, Dawei Qu, Lauryl M J Nutter, Colin McKerlie, Liane Hobson, Brenda Kick, Bonnie Lyons, Jean-Paul Wiegand, Rosalinda Doty, Juan Antonio Aguilar-Pimentel, Martin Hrabe de Angelis, Mary Dickinson, John Seavitt, Jacqueline K White, Cheryl L Scudamore, and Sara Wells
- Subjects
Medicine ,Science - Abstract
Dislocation in hindlimb tarsals are being observed at a low, but persistent frequency in group-housed adult male mice from C57BL/6N substrains. Clinical signs included a sudden onset of mild to severe unilateral or bilateral tarsal abduction, swelling, abnormal hindlimb morphology and lameness. Contraction of digits and gait abnormalities were noted in multiple cases. Radiographical and histological examination revealed caudal dislocation of the calcaneus and partial dislocation of the calcaneoquartal (calcaneus-tarsal bone IV) joint. The detection, frequency, and cause of this pathology in five large mouse production and phenotyping centres (MRC Harwell, UK; The Jackson Laboratory, USA; The Centre for Phenogenomics, Canada; German Mouse Clinic, Germany; Baylor College of Medicine, USA) are discussed.
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- 2020
- Full Text
- View/download PDF
3. A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction
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Michael R. Bowl, Michelle M. Simon, Neil J. Ingham, Simon Greenaway, Luis Santos, Heather Cater, Sarah Taylor, Jeremy Mason, Natalja Kurbatova, Selina Pearson, Lynette R. Bower, Dave A. Clary, Hamid Meziane, Patrick Reilly, Osamu Minowa, Lois Kelsey, The International Mouse Phenotyping Consortium, Glauco P. Tocchini-Valentini, Xiang Gao, Allan Bradley, William C. Skarnes, Mark Moore, Arthur L. Beaudet, Monica J. Justice, John Seavitt, Mary E. Dickinson, Wolfgang Wurst, Martin Hrabe de Angelis, Yann Herault, Shigeharu Wakana, Lauryl M. J. Nutter, Ann M. Flenniken, Colin McKerlie, Stephen A. Murray, Karen L. Svenson, Robert E. Braun, David B. West, K. C. Kent Lloyd, David J. Adams, Jacqui White, Natasha Karp, Paul Flicek, Damian Smedley, Terrence F. Meehan, Helen E. Parkinson, Lydia M. Teboul, Sara Wells, Karen P. Steel, Ann-Marie Mallon, and Steve D. M. Brown
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Science - Abstract
The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.
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- 2017
- Full Text
- View/download PDF
4. Loss of Functionally Redundant p38 Isoforms in T Cells Enhances Regulatory T Cell Induction
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Morisada, Hayakawa, Hiroko, Hayakawa, Tsvetana, Petrova, Patcharee, Ritprajak, Ruhcha V, Sutavani, Guillermina Yanek, Jiménez-Andrade, Yasuyo, Sano, Min-Kyung, Choo, John, Seavitt, Ram K C, Venigalla, Kinya, Otsu, Katia, Georgopoulos, J Simon C, Arthur, and Jin Mo, Park
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Mice, Knockout ,MAP Kinase Signaling System ,TOR Serine-Threonine Kinases ,Immunology ,Receptors, Antigen, T-Cell ,Forkhead Transcription Factors ,p38 ,T-Lymphocytes, Regulatory ,Mitogen-Activated Protein Kinase 14 ,Mice ,Mitogen-Activated Protein Kinase 11 ,T-cell ,Animals ,mouse ,signal transduction - Abstract
The evolutionarily conserved protein kinase p38 mediates innate resistance to environmental stress and microbial infection. Four p38 isoforms exist in mammals and may have been co-opted for new roles in adaptive immunity. Murine T cells deficient in p38α, the ubiquitously expressed p38 isoform, showed no readily apparent cell-autonomous defects while expressing elevated amounts of another isoform, p38β. Mice with T cells simultaneously lacking p38α and p38β displayed lymphoid atrophy and elevated Foxp3+ regulatory T cell frequencies. Double deficiency of p38α and p38β in naïve CD4+ T cells resulted in an attenuation of MAPK-activated protein kinase (MK)-dependent mTOR signaling after T cell receptor engagement, and enhanced their differentiation into regulatory T cells under appropriate inducing conditions. Pharmacological inhibition of the p38-MK-mTOR signaling module produced similar effects, revealing potential for therapeutic applications.
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- 2016
5. Unconventional Potentiation of Gene Expression by Ikaros
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Elizabeth J. Heller, John Seavitt, Katia Georgopoulos, and Joseph Koipally
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Regulation of gene expression ,Base Sequence ,Cell Biology ,Biology ,Biochemistry ,Molecular biology ,DNA-binding protein ,Ikaros Transcription Factor ,Chromatin ,DNA-Binding Proteins ,Mice ,Gene Expression Regulation ,Microscopy, Fluorescence ,Transcription (biology) ,Gene expression ,Animals ,Humans ,Nucleosome ,Molecular Biology ,Transcription factor ,DNA Primers ,Transcription Factors - Abstract
Ikaros is essential for the normal development and regulated proliferation of lymphoid cells. In lymphocytes, Ikaros exists as an integral component of chromatin-remodeling complexes, including the Mi-2beta/nucleosome remodeling and deacetylation complex (NuRD) complex. It is expected that Ikaros, together with these associated activities effects repression, but here we show that they may also potentiate gene expression in cycling cells. Ikaros cannot activate transcription by itself; instead, it enhances the activity of both weak and strong activators. For this role in potentiation, Ikaros requires its DNA binding and dimerization domains. The DNA binding and dimerization properties of Ikaros are also responsible for its targeting to pericentromeric heterochromatin (PC-HC). Significantly, Ikaros mutants with altered specificity for DNA binding that are unable to localize to PC-HC are incapable of stimulating transcription from reporters bearing their cognate sites. Thus, potentiation of gene expression by Ikaros correlates strongly with its ability to localize to PC-HC in combination with the chromatin remodeler Mi-2beta.
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- 2002
6. CD45-associated protein is not essential for the regulation of antigen receptor-mediated signal transduction
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Chun Kung, Michelle Noll, John Seavitt, Jeanette T. Pingel, Matthew L. Thomas, Lynn S. White, and Meinoshin Okumura
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Thymocyte ,Transmembrane domain ,Immunology ,B-cell receptor ,T-cell receptor ,Immunology and Allergy ,Protein tyrosine phosphatase ,Signal transduction ,Biology ,Kinase activity ,Molecular biology ,Transmembrane protein ,Cell biology - Abstract
CD45 is a transmembrane protein tyrosine phosphatase required for signaling through the T-and B-cell antigen receptors. In lymphocytes, CD45 interacts with CD45-associated protein (CD45AP), a 32 000 Mr phosphoprotein, through their respective transmembrane domains. To determine whether CD45AP affects the ability of CD45 to regulate antigen receptor signaling, CD45AP-deficient mice were generated. Thymocyte development was grossly normal. Moreover, the cellularity of the thymus and spleens were normal. CD45 expression on thymocytes and splenocytes, ascertained by flow cytometry, was comparable between CD45AP-deficient mice and littermate controls. In contrast to a previous report (Matsuda et al., J. Exp. Med. 1998 187: 1863 - 1870). CD45AP-deficient and normal thymocytes and splenocytes proliferated similarly in response to various mitogens or antigen receptor cross-linking. Furthermore, thymocyte CD45-associated p56(lck) kinase activity was similar between CD45AP-deficient and normal cells. We conclude that CD45AP is not essential for the regulation of Src-family kinase activity by CD45.
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- 1999
7. Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis
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Taku Naito, Audrey F. Jackson, Marei Dose, John Seavitt, Jiangwen Zhang, Feifei Liu, Fotini Gounari, Howard T. Petrie, Elizabeth J. Heller, Toshimi Yoshida, Katia Georgopoulos, and Mariko Kashiwagi
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Cellular differentiation ,Immunology ,Article ,Chromatin remodeling ,03 medical and health sciences ,Ikaros Transcription Factor ,Mice ,0302 clinical medicine ,Immunology and Allergy ,Nucleosome ,Animals ,Gene Regulatory Networks ,Lymphocytes ,Nucleotide Motifs ,Transcription factor ,030304 developmental biology ,0303 health sciences ,Leukemia ,Thymocytes ,biology ,Base Sequence ,Gene Expression Profiling ,Cell Differentiation ,Chromatin Assembly and Disassembly ,Molecular biology ,Mi-2/NuRD complex ,Chromatin ,Cell biology ,Histone ,030220 oncology & carcinogenesis ,biology.protein ,Mi-2 Nucleosome Remodeling and Deacetylase Complex ,Protein Binding - Abstract
Cell fate depends on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2β nucleosome-remodeling and histone-deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid lineage-determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active genes encoding molecules involved in lymphoid differentiation. Loss of Ikaros DNA-binding activity caused a local increase in chromatin remodeling and histone deacetylation and suppression of lymphoid cell-specific gene expression. Without Ikaros, the NuRD complex also redistributed to transcriptionally poised genes that were not targets of Ikaros (encoding molecules involved in proliferation and metabolism), which induced their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks.
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- 2011
8. The Role of the Ikaros Gene Family in Lymphocyte Development
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Pablo Gómez-del Arco, Taku Naito, Katia Georgopoulos, Christine J. Williams, Toshimi Yoshida, and John Seavitt
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Zinc finger ,General transcription factor ,Gene expression ,Gene family ,Biology ,Gene ,Mi-2/NuRD complex ,Chromatin remodeling ,Chromatin ,Cell biology - Abstract
In many developmental systems, nuclear regulators have been implicated in coupling key events in gene expression with specific cell fate and lineage decisions. In the hemo-lymphoid system, the Ikaros gene family of zinc finger DNA binding factors controls lymphocyte specification and homeostasis from the hemopoietic stem cell (HSC) throughout development. The dependence of hemo-lymphoid differentiation on Ikaros DNA binding activity together with the presence of Ikaros proteins within higher order chromatin remodeling complexes supports the hypothesis that Ikaros plays a key role in the lineage-specific remodeling of chromatin. Association of Ikaros and its remodeling partners with the chromatin of key lineage-specific genes, and the dependence of these genes on Ikaros complexes for their expression supports this hypothesis and provides unique paradigms to study chromatin regulation of differentiation.
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- 2005
9. The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development
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Christine J. Williams, Katia Georgopoulos, Ulrich H. von Andrian, Piper Keables, Beverly De Souza, Susan M Cashman, Taku Naito, John Seavitt, Pablo Gómez-del Arco, and Xiaoqing Qi
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Transcriptional Activation ,Cellular differentiation ,T-Lymphocytes ,Immunology ,Receptors, Antigen, T-Cell ,Apoptosis ,Cell Cycle Proteins ,Mice, Transgenic ,Thymus Gland ,Biology ,Chromatin remodeling ,Histone Deacetylases ,Mice ,Acetyltransferases ,Basic Helix-Loop-Helix Transcription Factors ,Histone code ,Immunology and Allergy ,Animals ,p300-CBP Transcription Factors ,Transgenes ,ChIA-PET ,Cells, Cultured ,Histone Acetyltransferases ,Regulation of gene expression ,Cell Differentiation ,Chromatin Assembly and Disassembly ,Flow Cytometry ,Mi-2/NuRD complex ,Molecular biology ,Chromatin ,DNA-Binding Proteins ,Histone ,Infectious Diseases ,Enhancer Elements, Genetic ,Gene Expression Regulation ,CD4 Antigens ,biology.protein ,Cell Division ,Mi-2 Nucleosome Remodeling and Deacetylase Complex ,Transcription Factors - Abstract
Changes in chromatin structure underlie the activation or silencing of genes during development. The chromatin remodeler Mi-2beta is highly expressed in thymocytes and is presumed to be a transcriptional repressor because of its presence in the nucleosome remodeling deacetylase (NuRD) complex. Using conditional inactivation, we show that Mi-2beta is required at several steps during T cell development: for differentiation of beta selected immature thymocytes, for developmental expression of CD4, and for cell divisions in mature T cells. We further show that Mi-2beta plays a direct role in promoting CD4 gene expression. Mi-2beta associates with the CD4 enhancer as well as the E box binding protein HEB and the histone acetyltransferase (HAT) p300, enabling their recruitment to the CD4 enhancer and causing histone H3-hyperacetylation to this regulatory region. These findings provide important insights into the regulation of CD4 expression during T cell development and define a role for Mi-2beta in gene activation.
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- 2003
10. Erratum: Corrigendum: Aiolos promotes TH17 differentiation by directly silencing Il2 expression
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Katia Georgopoulos, Sheng Xiao, Meghan Nadeau, Ada Yeste, Deepak Kumar, Manu Rangachari, Vijay K. Kuchroo, Chen Zhu, Francisco J. Quintana, Hulin Jin, John Seavitt, and Evan J Burns
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Expression (architecture) ,Nat ,Immunology ,Immunology and Allergy ,Th17 differentiation ,Gene silencing ,Biology ,Bioinformatics ,Cell biology - Abstract
Nat. Immunol. 13, 770–777 (2012); published online 1 July 2012; corrected after print 21 September 2012 In the version of this article initially published, some data in the bottom right plot in Figure 3d were partially obscured. The error has been corrected in the HTML and PDF versions of the article.
- Published
- 2013
11. CD45
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John Seavitt and Matthew L. Thomas
- Published
- 1998
12. Gm614: A NOVEL X-LINKED GENE ASSOCIATED WITH MALE INFERTILITY IN MICE.
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Claire, Reynolds Anna, Harlie, Cope, Denise, Lanza, Isabel, Lorenzo, Ashley, Pawelka, Olga, Medina-Martinez, Matthew, Gonzalez, Cecilia, Ljungberg, Thomas, Garcia, John, Seavitt, and Jason, Heaney
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MALE infertility , *MICE , *GENES - Published
- 2024
- Full Text
- View/download PDF
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