RRC ID 5401
Author Omi N, Kiyokawa E, Matsuda M, Kinoshita K, Yamada S, Yamada K, Matsushima Y, Wang Y, Kawai J, Suzuki M, Hayashizaki Y, Hiai H.
Title Mutation of Dock5, a member of the guanine exchange factor Dock180 superfamily, in the rupture of lens cataract mouse.
Journal Exp Eye Res
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.
Volume 86(5)
Pages 828-34
Published 2008-5-1
DOI 10.1016/j.exer.2008.02.011
PII S0014-4835(08)00070-5
PMID 18396277
MeSH Animals Cataract / genetics* Cataract / metabolism Chromosome Mapping DNA, Complementary / genetics Disease Models, Animal Eye Proteins / biosynthesis Eye Proteins / genetics* Genes, Recessive Genetic Predisposition to Disease Guanine Nucleotide Exchange Factors / biosynthesis Guanine Nucleotide Exchange Factors / genetics* Haplotypes Lens, Crystalline / metabolism Male Mice Mice, Inbred BALB C Mutation* Polymerase Chain Reaction / methods RNA, Messenger / genetics Rupture, Spontaneous Signal Transduction
IF 3.011
Times Cited 17
Mice RBRC00209 RBRC00423 RBRC00432