title: Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice.
abstract: Gap junction channels formed by alpha3 (Cx46) and alpha8 (Cx50) connexin provide pathways for communication between the fiber cells in the normal transparent lens. To determine the specific role of alpha3 connexin in vivo, the alpha3 connexin gene was disrupted in mice. Although the absence of alpha3 connexin had no obvious influence on the early stages of lens formation and the differentiation of lens fibers, mice homozygous for the disrupted alpha3 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.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: X
authors.initials: X
authors.lastname: Gong
authors.forename: E
authors.initials: E
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Klier
authors.forename: Q
authors.initials: Q
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Lei
authors.forename: N M
authors.initials: NM
authors.lastname: Kumar
authors.forename: J
authors.initials: J
authors.lastname: Horwitz
authors.forename: N B
authors.initials: NB
authors.lastname: Gilula
mesh_terms: D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D017630:Connexins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007908:Lens, Crystalline / Q000254:growth & development / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D017630:Connexins; C082917:GJA3 protein, human; D001616:beta-Galactosidase