Loss of AND-34/BCAR3 Expression in Mice Results in Rupture of the Adult Lens

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dc.contributor.author Near, Richard I. en_US
dc.contributor.author Smith, Richard S. en_US
dc.contributor.author Toselli, Paul A. en_US
dc.contributor.author Freddo, Thomas F. en_US
dc.contributor.author Bloom, Alexander B. en_US
dc.contributor.author Vanden Borre, Pierre en_US
dc.contributor.author Seldin, David C. en_US
dc.contributor.author Lerner, Adam en_US
dc.date.accessioned 2012-01-11T21:40:12Z
dc.date.available 2012-01-11T21:40:12Z
dc.date.copyright 2009 en_US
dc.date.issued 2009-4-03 en_US
dc.identifier.citation Near, Richard I., Richard S. Smith, Paul A. Toselli, Thomas F. Freddo, Alexander B. Bloom, Pierre Vanden Borre, David C. Seldin, Adam Lerner. "Loss of AND-34/BCAR3 expression in mice results in rupture of the adult lens" Molecular Vision 15:685-699. (2009) en_US
dc.identifier.issn 1090-0535 en_US
dc.identifier.uri http://hdl.handle.net/2144/3224
dc.description.abstract PURPOSE. AND-34/BCAR3 (Breast Cancer Anti-Estrogen Resistance 3) associates with the focal adhesion adaptor protein, p130CAS/BCAR1. Expression of AND-34 regulates epithelial cell growth pattern, motility, and growth factor dependence. We sought to establish the effects of the loss of AND-34 expression in a mammalian organism. METHODS. AND-34−/− mice were generated by homologous recombination. Histopathology, in situ hybridization, and western blotting were performed on murine tissues. RESULTS. Western analyses confirmed total loss of expression in AND-34−/− splenic lymphocytes. Mice lacking AND-34 are fertile and have normal longevity. While AND-34 is widely expressed in wild type mice, histologic analysis of multiple organs in AND-34−/− mice is unremarkable and analyses of lymphocyte development show no overt changes. A small percentage of AND-34−/− mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber. Following initial vacuolization and liquefaction of the lens cortex first observed at postnatal day three, posterior lens rupture occurs in all AND-34−/− mice, beginning as early as three weeks and seen in all mice at three months. Western blot analysis and in situ hybridization confirmed the presence of AND-34 RNA and protein in lens epithelial cells, particularly at the lens equator. Prior data link AND-34 expression to the activation of Akt signaling. While Akt Ser 473 phosphorylation was readily detectable in AND-34+/+ lens epithelial cells, it was markedly reduced in the AND-34−/− lens epithelium. Basal levels of p130Cas phosphorylation were higher in AND-34+/+ than in AND-34−/− lens epithelium. CONCLUSIONS. These results demonstrate the loss of AND-34 dysregulates focal adhesion complex signaling in lens epithelial cells and suggest that AND-34-mediated signaling is required for maintenance of the structural integrity of the adult ocular lens. en_US
dc.description.sponsorship National Institutes of Health (RO1 CA114094); Logica Foundation en_US
dc.language.iso en en_US
dc.publisher Molecular Vision en_US
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/3.0/ en_US
dc.title Loss of AND-34/BCAR3 Expression in Mice Results in Rupture of the Adult Lens en_US
dc.type article en_US
dc.identifier.pubmedid 19365570 en_US
dc.identifier.pmcid 2666772 en_US

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