Omi Natsue, Kiyokawa Etsuko, Matsuda Michiyuki, Kinoshita Kazuo, Yamada Shuichi, Yamada Kazumi, Matsushima Yoshibumi, Wang Yun, Kawai Jun, Suzuki Masanori, Hayashizaki Yoshihide, Hiai Hiroshi
Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Exp Eye Res. 2008 May;86(5):828-34. doi: 10.1016/j.exer.2008.02.011. Epub 2008 Mar 2.
Rupture of lens cataract (RLC) in the mouse is a spontaneous mutation inherited by a single autosomal recessive gene mapped on chromosome 14. Fine mapping of the mutant locus revealed a nucleotide deletion of 27-bp at the end of 15th exon of Dock5 (Dedicator of cytokinesis-5), a member of the Dock gene superfamily. Since the deletion occurred in-frame, the RLC-DOCK5 protein had a deletion of 9 amino acids (a.a. 506-514) in the DHR1 (DOCK homology region-1) domain that is essential for DOCK5, a GTP-exchanger for Rac1. Although Dock5 mRNA was intensely expressed equally in mutant and wild-type lenses, DOCK5 protein was hardly detectable in the mutant lens. In contrast, expression of Dock180, another member of Dock subfamily A, was not affected in RLC. Immunohistochemically, DOCK5 was stained intensely in the cytoplasm of the anterior epithelial cells and weakly in lens fiber of the wild type lenses, but little in RLC lens. These observations suggest that the mutation may somehow destabilize DOCK5 protein. We propose to designate the mutant allele of rlc as Dock5rlc. Relevance of the signaling pathway involving DOCK5-RAC1 in maintenance of lens integrity of growing lens is discussed.
小鼠晶状体破裂性白内障（RLC）是一种由位于14号染色体上的单个常染色体隐性基因遗传的自发突变。对突变位点的精细定位显示，Dock5（细胞分裂素 dedicator-5）第15外显子末端有一个27 bp的核苷酸缺失，Dock5是Dock基因超家族的成员。由于缺失发生在阅读框内，RLC-DOCK5蛋白在对Rac1起GTP交换作用的DOCK5所必需的DHR1（DOCK同源区域-1）结构域中缺失了9个氨基酸（第506 - 514位氨基酸）。尽管Dock5 mRNA在突变型和野生型晶状体中均强烈且等量表达，但在突变型晶状体中几乎检测不到DOCK5蛋白。相比之下，Dock亚家族A的另一个成员Dock180的表达在RLC中未受影响。免疫组织化学显示，野生型晶状体的前上皮细胞胞质中DOCK5染色强烈，晶状体纤维中染色较弱，而在RLC晶状体中几乎没有染色。这些观察结果表明，该突变可能以某种方式使DOCK5蛋白不稳定。我们建议将rlc的突变等位基因命名为Dock5rlc。文中讨论了涉及DOCK5 - RAC1的信号通路在维持生长中晶状体完整性方面的相关性。
