Pde6b rd1 mutation modifies cataractogenesis in Foxe3 rct mice

Abstract The Foxe3 rct 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 Pde6b rd1 mutation, which induced degeneration of the photoreceptor cells, is a strong candidate genetic modifier to accelerate the severity of cataractogenesis of Foxe3 rct mice. We created congenic mice by transferring a genomic region including the Foxe3 rct mutation to the B6 genetic background, which does not carry the Pde6b rd1 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- Foxe3 rct 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- Foxe3 rct mice. These results clearly show that the development of early-onset cataracts requires at least two mutant alleles of Foxe3 rct and Pde6b rd1 , and another modifier associated with the severity of cataract phenotypes in Foxe3 rct mice underlies the genetic backgrounds in mice.