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21 results on '"Vizor, Lucie"'

3. Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features

Author

Tucci, Valter, Kleefstra, Tjitske, Hardy, Andrea, Heise, Ines, Maggi, Silvia, Willemsen, Marjolein H., Hilton, Helen, Esapa, Chris, Simon, Michelle, Beunavista, Maria-Teresa, McGuffin, Liam J., Vizor, Lucie, Dodero, Luca, Tsaftaris, Sotirios, Romero, Rosario, Nillesen, Willy N., Vissers, Lisenka E.L.M., Kempers, Marlies J., Vulto-van Silfhout, Anneke T., Iqbal, Zafar, Orlando, Marta, Maccione, Alessandro, Lassi, Glenda, Farisello, Pasqualina, Contestabile, Andrea, Tinarelli, Federico, Nieus, Thierry, Raimondi, Andrea, Greco, Barbara, Cantatore, Daniela, Gasparini, Laura, Berdondini, Luca, Bifone, Angelo, Gozzi, Alessandro, Wells, Sara, and Nolan, Patrick M.

Subjects
Gene mutations -- Research, Cadherins -- Genetic aspects -- Research, Mental retardation -- Genetic aspects -- Causes of -- Research, Health care industry
Abstract

The recent identification of multiple dominant mutations in the gene encoding β-catenin in both humans and mice has enabled exploration of the molecular and cellular basis of β-catenin function in cognitive impairment. In humans, β-catenin mutations that cause a spectrum of neurodevelopmental disorders have been identified. We identified de novo β-catenin mutations in patients with intellectual disability, carefully characterized their phenotypes, and were able to define a recognizable intellectual disability syndrome. In parallel, characterization of a chemically mutagenized mouse line that displays features similar to those of human patients with β-catenin mutations enabled us to investigate the consequences of β-catenin dysfunction through development and into adulthood. The mouse mutant, designated batface (Bfc), carries a Thr653Lys substitution in the C-terminal armadillo repeat of β-catenin and displayed a reduced affinity for membrane-associated cadherins. In association with this decreased cadherin interaction, we found that the mutation results in decreased intrahemispheric connections, with deficits in dendritic branching, long-term potentiation, and cognitive function. Our study provides in vivo evidence that dominant mutations in β-catenin underlie losses in its adhesion-related functions, which leads to severe consequences, including intellectual disability, childhood hypotonia, progressive spasticity of lower limbs, and abnormal craniofacial features in adults., Introduction β-Catenin (CTNNB1) is a highly conserved protein that implements key cellular functions by interacting with cell-adhesion proteins, signaling molecules, and transcription factors (1). The characteristic structural feature of the [...]

Published
2014
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4. Zfhx3-Mediated Genetic Ablation of the Mouse SCN Abolishes Light Entrainable Circadian Activity While the Food Entrainable Oscillator Remains Intact

Author

Wilcox, Ashleigh G., primary, Bains, Rasneer Sonia, additional, Williams, Debbie, additional, Joynson, Elizabeth, additional, Vizor, Lucie, additional, Oliver, Peter L., additional, Maywood, Elizabeth S., additional, Hastings, Michael H., additional, Banks, Gareth, additional, and Nolan, Patrick M., additional

Published
2021
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5. A gene-driven ENU-based approach to generating an allelic series in any gene

Author

Quwailid, Mohamed Mohideen, Hugill, Alison, Dear, Neil, Vizor, Lucie, Wells, Sara, Horner, Emma, Fuller, Shelly, Weedon, Jessica, McMath, Hamish, Woodman, Paul, Edwards, David, Campbell, David, Rodger, Susan, Carey, Joanne, Roberts, Ann, Glenister, Pete, Lalanne, Zuzanna, Parkinson, Nick, Coghill, Emma L., McKeone, Richard, Cox, Sam, Willan, John, Greenfield, Andy, Keays, David, Brady, Saffron, Spurr, Nigel, Gray, Ian, Hunter, Jackie, Brown, Steve D.M., and Cox, Roger D.

Published
2004
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6. Novel phenotypes identified by plasma biochemical screening in the mouse

Author

Hough, Tertius A., Nolan, Patrick M., Tsipouri, Vicky, Toye, Ayo A., Gray, Ian C., Goldsworthy, Michelle, Moir, Lee, Cox, Roger D., Clements, Sian, Glenister, Peter H., Wood, John, Selley, Rachael L., Strivens, Mark A., Vizor, Lucie, McCormack, Stefan L., Peters, Josephine, Fisher, Elizabeth M., Spurr, Nigel, Rastan, Sohaila, Martin, Joanne E., Brown, Steve D.M., and Jacqueline Hunter, A.

Published
2002
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11. HIF–VEGF Pathways Are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants

Author

Avraham, Karen B., Cheeseman, Michael T., Tyrer, Hayley, Williams, Debbie, Hough, Tertius A., Pathak, Paras, Romero, Maria R., Hilton, Helen, Bali, Sulzhan, Parker, Andrew, Vizor, Lucie, Purnell, Tom, Vowell, Kate, Wells, Sara, Bhutta, Mahmood F., Potter, Paul K., and Brown, Steve D. M.

Subjects
Vascular Endothelial Growth Factor A, Cancer Research, Indoles, Pyridines, Angiogenesis, STREPTOCOCCUS-PNEUMONIAE, Gene Expression, QH426-470, Pathogenesis, Mice, Blister, Sunitinib, Genetics (clinical), GENE-EXPRESSION, Mice, Inbred C3H, MIDDLE-EAR EFFUSION, Cell Hypoxia, Body Fluids, Lymphangiogenesis, Vascular endothelial growth factor A, Hypoxia-inducible factors, Nitroimidazoles, Medicine, medicine.symptom, Research Article, Signal Transduction, Drugs and Devices, HYPOXIA-INDUCIBLE FACTOR, Ear, Middle, Inflammation, KAPPA-B, Biology, Model Organisms, Downregulation and upregulation, SECRETORY OTITIS, NONTYPABLE HAEMOPHILUS-INFLUENZAE, medicine, Genetics, Animals, Humans, Pyrroles, HSP90 Heat-Shock Proteins, Gene Networks, Hearing Loss, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Otitis Media with Effusion, A100, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Mutant Strains, Mice, Inbred C57BL, Disease Models, Animal, Receptors, Vascular Endothelial Growth Factor, Otorhinolaryngology, Gene Expression Regulation, ENDOTHELIAL GROWTH-FACTOR, Genetics of Disease, Immunology, INNATE IMMUNITY, Phthalazines, INFLAMMATORY MEDIATORS
Abstract

Otitis media with effusion (OME) is the commonest cause of hearing loss in children, yet the underlying genetic pathways and mechanisms involved are incompletely understood. Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chronic OME, but the mechanism by which they work remains uncertain. As hypoxia is a common feature of inflamed microenvironments, moderation of hypoxia may be a significant contributory mechanism. We have investigated the occurrence of hypoxia and hypoxia-inducible factor (HIF) mediated responses in Junbo and Jeff mouse mutant models, which develop spontaneous chronic otitis media. We found that Jeff and Junbo mice labeled in vivo with pimonidazole showed cellular hypoxia in inflammatory cells in the bulla lumen, and in Junbo the middle ear mucosa was also hypoxic. The bulla fluid inflammatory cell numbers were greater and the upregulation of inflammatory gene networks were more pronounced in Junbo than Jeff. Hif-1α gene expression was elevated in bulla fluid inflammatory cells, and there was upregulation of its target genes including Vegfa in Junbo and Jeff. We therefore investigated the effects in Junbo of small-molecule inhibitors of VEGFR signaling (PTK787, SU-11248, and BAY 43-9006) and destabilizing HIF by inhibiting its chaperone HSP90 with 17-DMAG. We found that both classes of inhibitor significantly reduced hearing loss and the occurrence of bulla fluid and that VEGFR inhibitors moderated angiogenesis and lymphangiogenesis in the inflamed middle ear mucosa. The effectiveness of HSP90 and VEGFR signaling inhibitors in suppressing OM in the Junbo model implicates HIF–mediated VEGF as playing a pivotal role in OM pathogenesis. Our analysis of the Junbo and Jeff mutants highlights the role of hypoxia and HIF–mediated pathways, and we conclude that targeting molecules in HIF–VEGF signaling pathways has therapeutic potential in the treatment of chronic OM., Author Summary Otitis media with effusion (OME) is the commonest cause of hearing loss in children, and treatment using grommets remains the commonest surgical procedure in children. Chronic forms of OM are known from human population studies to have a significant genetic component, but little is known of the underlying genes or pathways involved. We have analyzed two chronic OM mouse models, the Junbo and Jeff mutants, and have found that both demonstrate hypoxia and hypoxia-inducible factor (HIF) mediated responses. There is upregulation of inflammatory pathways in the mutant middle ears and in Junbo elevation of cytokines that modulate Hif-1α. Hif-1α levels are raised in the middle ear as well as downstream targets of HIF such as Vegfa. We explored the effects of small-molecule inhibitors of HSP90 and VEGF receptor signaling in the Junbo mutant and found significant reductions in hearing loss, the occurrence of bulla fluid, and moderation of vascular changes in the inflamed middle ear mucosa with the VEGF receptor inhibitors. The study of the Junbo and Jeff mutants demonstrates the role of hypoxia and HIF mediated pathways in OM pathogenesis, and it indicates that targeting the HIF–VEGF pathway may represent a novel approach to therapeutic intervention in chronic OM.

Published
2011

12. HIF–VEGF Pathways Are Critical for Chronic Otitis Media in Junbo and Jeff Mouse Mutants

Author

Cheeseman, Michael T., primary, Tyrer, Hayley E., additional, Williams, Debbie, additional, Hough, Tertius A., additional, Pathak, Paras, additional, Romero, Maria R., additional, Hilton, Helen, additional, Bali, Sulzhan, additional, Parker, Andrew, additional, Vizor, Lucie, additional, Purnell, Tom, additional, Vowell, Kate, additional, Wells, Sara, additional, Bhutta, Mahmood F., additional, Potter, Paul K., additional, and Brown, Steve D. M., additional

Published
2011
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14. Novel Mouse Model of Autosomal Semidominant Adult Hypophosphatasia Has a Splice Site Mutation in the Tissue Nonspecific Alkaline Phosphatase Gene Akp2

Author

Hough, Tertius A, primary, Polewski, Monika, additional, Johnson, Kristen, additional, Cheeseman, Michael, additional, Nolan, Patrick M, additional, Vizor, Lucie, additional, Rastan, Sohaila, additional, Boyde, Alan, additional, Pritzker, Kenneth, additional, Hunter, A Jackie, additional, Fisher, Elizabeth MC, additional, Terkeltaub, Robert, additional, and Brown, Steve DM, additional

Published
2007
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15. Three Novel Pigmentation Mutants Generated by Genome-Wide Random ENU Mutagenesis in the Mouse

Author

Tsipouri, Vicky, primary, Curtin, John A., additional, Nolan, Pat M., additional, Vizor, Lucie, additional, Parsons, Claire A., additional, Clapham, Colin M., additional, Latham, Ian D., additional, Rooke, Lesley J., additional, Martin, Jo E., additional, Peters, Jo, additional, Hunter, A. Jackie, additional, Rogers, Derek, additional, Rastan, Sohaila, additional, Brown, Steve D.M., additional, Fisher, Elizabeth M.C., additional, Spurr, Nigel K., additional, and Gray, Ian C., additional

Published
2004
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17. A Mutation inAf4Is Predicted to Cause Cerebellar Ataxia and Cataracts in the Robotic Mouse

Author

Isaacs, Adrian M., primary, Oliver, Peter L., additional, Jones, Emma L., additional, Jeans, Alexander, additional, Potter, Allyson, additional, Hovik, Berit H., additional, Nolan, Patrick M., additional, Vizor, Lucie, additional, Glenister, Peter, additional, Simon, A. Katharina, additional, Gray, Ian C., additional, Spurr, Nigel K., additional, Brown, Steve D. M., additional, Hunter, A. Jackie, additional, and Davies, Kay E., additional

Published
2003
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20. A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse

Author

Nolan, Patrick M., primary, Peters, Jo, additional, Strivens, Mark, additional, Rogers, Derek, additional, Hagan, Jim, additional, Spurr, Nigel, additional, Gray, Ian C., additional, Vizor, Lucie, additional, Brooker, Debra, additional, Whitehill, Elaine, additional, Washbourne, Rebecca, additional, Hough, Tertius, additional, Greenaway, Simon, additional, Hewitt, Mazda, additional, Liu, Xinhong, additional, McCormack, Stefan, additional, Pickford, Karen, additional, Selley, Rachael, additional, Wells, Christine, additional, Tymowska-Lalanne, Zuzanna, additional, Roby, Phil, additional, Glenister, Peter, additional, Thornton, Claire, additional, Thaung, Caroline, additional, Stevenson, Julie-Anne, additional, Arkell, Ruth, additional, Mburu, Philomena, additional, Hardisty, Rachel, additional, Kiernan, Amy, additional, Erven, Alexandra, additional, Steel, Karen P., additional, Voegeling, Stephanie, additional, Guenet, Jean-Louis, additional, Nickols, Carole, additional, Sadri, Ramin, additional, Naase, Mahmood, additional, Isaacs, Adrian, additional, Davies, Kay, additional, Browne, Mick, additional, Fisher, Elizabeth M.C., additional, Martin, Jo, additional, Rastan, Sohaila, additional, Brown, Steve D.M., additional, and Hunter, Jackie, additional

Published
2000
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21. A Mutation in Af4 Is Predicted to Cause Cerebellar Ataxia and Cataracts in the Robotic Mouse.

Author

Isaacs, Adrian M., Oliver, Peter L., Jones, Emma L., Jeans, Alexander, Potter, Allyson, Hovik, Berit H., Nolan, Patrick M., Vizor, Lucie, Glenister, Peter, Simon, A. Katharina, Gray, Ian C., Spurr, Nigel H., Brown, Steve D.M., Hunter, A. Jackie, and Davies, Kay E.

Subjects
ROBOTICS, PURKINJE cells, CEREBELLAR ataxia, NEURODEGENERATION, ATAXIA
Abstract

Presents information on a study which demonstrated a mutant mouse model for cerebellar ataxia that develops Purkinje cell loss in a stereotypical region-specific manner. Histology and immunohistochemistry; Identification of robotic mice which develop region-specific Purkinje cell loss; Neurodegenerative changes in the robotic cerebellum.

Published
2003
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