DISRUPTION OF ALPHA(3) CONNEXIN GENE LEADS TO PROTEOLYSIS AND CATARACTOGENESIS IN MICE

Gap junction channels formed by alpha(3) (Cx46) and alpha(8) (Cx50) co nnexin provide pathways for communication between the fiber cells in t he normal transparent lens. To determine the specific role of alpha(3) connexin in vivo, the alpha(3) connexin gene was disrupted in mice. A lthough the absence of alpha(3) connexin had no obvious influence on t he early stages of lens formation and the differentiation of lens fibe rs, mice homozygous for the disrupted alpha(3) gene developed nuclear cataracts that were associated with the proteolysis of crystallins. Th is study establishes the importance of gap junctions in maintaining no rmal lens transparency by providing a cell-cell signaling pathway or s tructural component for the proper organization of lens membrane and c ytoplasmic proteins.