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Dwan A. Gerido, Caterina Sellitto, Leping Li, Thomas W. White; Genetic Background Influences Cataractogenesis, but Not Lens Growth Deficiency, in Cx50-Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2003;44(6):2669-2674. doi: 10.1167/iovs.02-1311.
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purpose. Deletion of connexin (Cx)50 produces microphthalmia with nuclear cataracts. To determine whether these two traits are influenced by genetic background and are dependent on each other, mice carrying the Cx50 deletion in two different strains were generated, and the growth defect and severity of cataracts were analyzed.
methods. Cx50-knockout mice were generated in the 129S6 strain, and back-crossed into the C57BL/6J genetic background. To analyze the influence of genetic background on the observed phenotype, postnatal lens growth, lens clarity, lens histology and crystallin solubility were determined and compared between the two strains of Cx50-knockout mice.
results. The growth deficiency persisted, regardless of genetic background, but genetic modifiers that differentially altered the solubility of crystallin proteins influenced the severity of cataracts. Expression levels of Cx46 were similar in all animals, regardless of genetic background, indicating that the differences were not due to a compensatory upregulation of Cx46.
conclusions. Taken together, these data indicate that the two components of the Cx50 phenotype are independent of each other and that cataractogenesis is under the influence of an unidentified genetic modifier.
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