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
|
WOS Category
|
OPHTHALMOLOGY
|
Resource |
Mice |
RBRC00209
RBRC00423
RBRC00432 |