RRC ID 50037
Author Wada K, Saito J, Yamaguchi M, Seki Y, Furugori M, Takahashi G, Nishito Y, Matsuda H, Shitara H, Kikkawa Y.
Title Pde6brd1 mutation modifies cataractogenesis in Foxe3rct mice.
Journal Biochem. Biophys. Res. Commun.
Abstract The Foxe3rct mutation, which causes early-onset cataracts, is a recessive mutation found in SJL/J mice. A previous study reported that cataract phenotypes are modified by the genetic background of mouse inbred strains and that the Pde6brd1 mutation, which induced degeneration of the photoreceptor cells, is a strong candidate genetic modifier to accelerate the severity of cataractogenesis of Foxe3rct mice. We created congenic mice by transferring a genomic region including the Foxe3rct mutation to the B6 genetic background, which does not carry the Pde6brd1 mutation. In the congenic mice, the cataract phenotypes became remarkably mild, and the development of cataracts was suppressed for a long time. Moreover, we created transgenic mice by injecting BAC clones including the wild-type Pde6b gene into the eggs of SJL-Foxe3rct mice. Although the resistant effect for cataract phenotypes in transgenic mice was less than that in congenic mice, the severity and onset time of cataract phenotypes were clearly improved and delayed, respectively, compared with the phenotypes of the original SJL-Foxe3rct mice. These results clearly show that the development of early-onset cataracts requires at least two mutant alleles of Foxe3rct and Pde6brd1, and another modifier associated with the severity of cataract phenotypes in Foxe3rct mice underlies the genetic backgrounds in mice.
Volume 496(1)
Pages 231-237
Published 2018-1-29
DOI 10.1016/j.bbrc.2018.01.031
PII S0006-291X(18)30037-8
PMID 29317205
MeSH Animals Cataract / genetics* Cataract / metabolism* Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics* Cyclic Nucleotide Phosphodiesterases, Type 6 / metabolism* Disease Progression Forkhead Transcription Factors / genetics* Forkhead Transcription Factors / metabolism* Genetic Predisposition to Disease / genetics* Mice Mice, Inbred C57BL Mice, Transgenic Structure-Activity Relationship
IF 2.559
Resource
DNA material MSM Mouse BAC clone MSMg01-521B08 (RDB04214)