TARGETED ABLATION OF CONNEXIN50 IN MICE RESULTS IN MICROPHTHALMIA ANDZONULAR PULVERULENT CATARACTS

In the ocular lens, gap junctional communication is a key component of homeostatic mechanisms preventing cataract formation. Gap junctions i n rodent lens fibers contain two known intercellular channel-forming-p roteins, connexin50 (Cx50) and Cx46. Since targeted ablation of Cx46 h as been shown to cause senile-type nuclear opacities, it appears that Cx50 alone cannot meet homeostatic requirements. To determine if lens pathology arises from a reduction in levels of communication or the lo ss of a connexin-specific function, we have generated mice with a targ eted deletion of the Cx50 gene. Cx50-null mice exhibited microphthalmi a and nuclear cataracts. At postnatal day 14 (P14), Cx50-knockout eyes weighed 32% less than controls, whereas lens mass was reduced by 46%. Cx50-knockout lenses also developed zonular pulverulent cataracts, an d lens abnormalities were detected by P7. Deletion of Cx50 did not alt er the amounts or distributions of Cx46 or Cx43, a component of lens e pithelial junctions. In addition, intercellular passage of tracers rev ealed the persistence of communication between all cell types in the C x50-knockout lens. These results demonstrate that Cx50 is required not only for maintenance of lens transparency but also for normal eye gro wth. Furthermore, these data indicate that unique functional propertie s of both Cx46 and Cx50 are required for proper lens development.