Rat Mutations cvd and hob with Cerebellar Malformations Map to Chromosome 2

摘要

In this paper, we executed genome mapping and comparative mapping analyses for cvd and hob, autosomal recessive mutations with cerebellar vermis defect and cerebellar dysplasia in the rat. For the linkage analysis, we produced three sets of backcross progeny, (ACI x CVD)F_1 and (F344 x CVD)F_1 females crossed to a cvd homozygous male rat, and (HOB x WKY)F_1 males crossed to hob homozygous female rats. Analysis of the segregation patterns of simple sequence length polymorphism (SSLP) markers scanning the whole rat genome allowed the mapping of these autosomal recessive mutations to rat Chromosome (Chr) 2. The most likely gene order is D2Mgh12 - D2Rat86 -D2Mit15 - D2Rat185 - cvd - D2Rat66 - D2Mgh13, and D2MH18 - Fga - D2Mit14 - D2Rat16 -hob - D2Mgh 13. Crossing test between a proven cvd heterozygous and a hob heterozygous rats demonstrated their allelism. Furthermore, comparative mapping indicated the cvd locus corresponds to mouse chromosome 3 and a strong candidate gene Unc5h3, a causative gene for the rostral cerebellar malformation mouse, was implicated.