| First Author | Tang Y | Year | 2007 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 48 |
| Issue | 6 | Pages | 2685-94 |
| PubMed ID | 17525200 | Mgi Jnum | J:123279 |
| Mgi Id | MGI:3717943 | Doi | 10.1167/iovs.06-0926 |
| Citation | Tang Y, et al. (2007) Age-related cataracts in alpha3Cx46-knockout mice are dependent on a calpain 3 isoform. Invest Ophthalmol Vis Sci 48(6):2685-94 |
| abstractText | PURPOSE: Previous studies have demonstrated that in 129alpha3Cx46-/- mice, age-related nuclear cataract is formed. In the present study, a more in vivo-relevant model was generated to test the hypothesis that the calpain 3 gene is involved in age-related nuclear cataractogenesis in alpha3Cx46 knockout mice. METHODS: To test the hypothesis that the calpain 3 gene is involved in age-related nuclear cataractogenesis in alpha3Cx46 knockout mice, 129alpha3Cx46-/- and CAPN3-/- mice were mated to generate homozygous double-knockout (dKO) mice. Lenses from the mice were examined by visual observation, laser scan analysis, and histologic and biochemical methods. RESULTS: In the absence of the CAPN3 gene, the formation of a cataract was delayed, and its appearance was changed to a more diffuse, pulverulent type. Unlike in the 129alpha3Cx46-/- mouse, cleavage of gamma-crystallin was not detected in the dKO mouse. In both 129alpha3Cx46-/- and dKO mice, total Ca2+ increased. CONCLUSIONS: The present study shows for the first time that calpain 3 is necessary for the formation of age-dependent nuclear cataracts in alpha3Cx46-/- mice. Evidence that the calpain 3 gene is directly involved in, or part of the pathway that leads to, gamma-crystallin cleavage is presented. These results are consistent with the hypothesis that the loss of alpha3Cx46 leads to increased levels of Ca2+ ions, and this increase activates the CAPN3 isoform, Lp82/85, which results in the formation of a nuclear cataract. |
