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) connexin provide pathways for communication between the fiber cells in the normal transparent lens. To determine the specific role of alpha(3) connexin in vivo, the alpha(3) connexin gene was disrupted in mice. Although the absence of alpha(3) connexin had no obvious influence on the early stages of lens formation and the differentiation of lens fibers, mice homozygous for the disrupted alpha(3) gene developed nuclear cataracts that were associated with the proteolysis of crystallins. This study establishes the importance of gap junctions in maintaining normal lens transparency by providing a cell-cell signaling pathway or structural component for the proper organization of lens membrane and cytoplasmic proteins.