摘要：We found a novel spontaneous mouse mutant with depigmentation in the ventral body, which we called White Spotting (WS) mouse. Genetic investigation revealed deletion of a > 1.2-Mb genomic region containing nine genes ( Kit , Kdr , Srd5a3 , Tmeme165 , Clock , Pdcl2 , Nmu , Exoc1 , and Cep135 ). We designated this mutant allele Kit WS . Interestingly, homozygous mutants ( Kit WS/WS ) showed a peri-implantation lethal phenotype. Expression analyses of these nine genes in blastocysts suggested that Exoc1 was a prime candidate for this phenotype. We produced Exoc1 knockout mice, and the same peri-implantation lethal phenotype was seen in Exoc1 −/− embryos. In addition, the polygenic effect without Exoc1 was investigated in genome-edited Kit WE mice carrying the Mb-scale deletion induced by the CRISPR/Cas9 system. As Kit WE/WE embryos did not exhibit the abnormal phenotype, which was seen in Kit WS/WS . We concluded that peri-implantation lethality in Kit WS/WS was caused by a monogenic defect of Exoc1 .
