Disruption of alpha(3) connexin gene leads to proteolysis and cataractogenesis in mice

被引:354
作者
Gong, XH
Li, E
Klier, G
Huang, QL
Wu, Y
Lei, H
Kumar, NM
Horwitz, J
Gilula, NB
机构
[1] Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA 92037 USA
[2] HARVARD UNIV, MGH, SCH MED, CARDIOVASC RES CTR, CHARLESTOWN, MA 02129 USA
[3] UNIV CALIF LOS ANGELES, JULES STEIN EYE INST, LOS ANGELES, CA 90095 USA
关键词
D O I
10.1016/S0092-8674(00)80471-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:833 / 843
页数:11
相关论文
共 52 条
  • [1] Distribution and type of morphological damage in human nuclear age-related cataracts
    AlGhoul, KJ
    Lane, CW
    Taylor, VL
    Fowler, WC
    Costello, MJ
    [J]. EXPERIMENTAL EYE RESEARCH, 1996, 62 (03) : 237 - 251
  • [2] Chromatin degradation in differentiating fiber cells of the eye lens
    Bassnett, S
    Mataic, D
    [J]. JOURNAL OF CELL BIOLOGY, 1997, 137 (01) : 37 - 49
  • [3] BLOEMENDAL H, 1981, MOL CELLULAR BIOL EY, P85
  • [4] Bond J, 1996, INVEST OPHTH VIS SCI, V37, P1557
  • [5] A BETA-GALACTOSIDASE HYBRID PROTEIN TARGETED TO NUCLEI AS A MARKER FOR DEVELOPMENTAL STUDIES
    BONNEROT, C
    ROCANCOURT, D
    BRIAND, P
    GRIMBER, G
    NICOLAS, JF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (19) : 6795 - 6799
  • [6] BONNEROT C, 1993, METHOD ENZYMOL, V225, P451
  • [7] Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin
    Brady, JP
    Garland, D
    DuglasTabor, Y
    Robison, WG
    Groome, A
    Wawrousek, EF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (03) : 884 - 889
  • [8] ACTIVATION OF THE GAMMA-E-CRYSTALLIN PSEUDOGENE IN THE HUMAN HEREDITARY COPPOCK-LIKE CATARACT
    BRAKENHOFF, RH
    HENSKENS, HAM
    VANROSSUM, MWPC
    LUBSEN, NH
    SCHOENMAKERS, JGG
    [J]. HUMAN MOLECULAR GENETICS, 1994, 3 (02) : 279 - 283
  • [9] Connections with connexins: The molecular basis of direct intercellular signaling
    Bruzzone, R
    White, TW
    Paul, DL
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1996, 238 (01): : 1 - 27
  • [10] CONVERSION OF THE SUBSTRATE-SPECIFICITY OF MOUSE PROTEINASE GRANZYME-B
    CAPUTO, A
    JAMES, MNG
    POWERS, JC
    HUDIG, D
    BLEACKLEY, RC
    [J]. NATURE STRUCTURAL BIOLOGY, 1994, 1 (06): : 364 - 367