title: Mutation of Dock5, a member of the guanine exchange factor Dock180 superfamily, in the rupture of lens cataract mouse.
abstract: 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.
authors.affiliation: Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
authors.forename: Natsue
authors.initials: N
authors.lastname: Omi
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kiyokawa
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Matsuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Yoshibumi
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Kawai
authors.forename: Masanori
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiai
mesh_terms: D000818:Animals; D002386:Cataract / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis / Q000235:genetics*; D006239:Haplotypes; D007908:Lens, Crystalline / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012422:Rupture, Spontaneous; D015398:Signal Transduction
chemical_list: D018076:DNA, Complementary; C531318:Dock5 protein, mouse; D005136:Eye Proteins; D020662:Guanine Nucleotide Exchange Factors; D012333:RNA, Messenger