Journal Article Peri-implantation lethality in mice carrying megabase-scale deletion on 5qc3.3 is caused by Exoc1 null mutation

Mizuno, Seiya  ,  Takami, Kohei  ,  Daitoku, Yoko  ,  Tanimoto, Yoko  ,  Tra Thi Huong Dinh  ,  Mizuno-Iijima, Saori  ,  Hasegawa, Yoshikazu  ,  Takahashi, Satoru  ,  Sugiyama, Fumihiro  ,  Yagami, Ken-ichi

5p.13632 , 2015-09 , Nature Publishing Group
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 KitWS. Interestingly, homozygous mutants (KitWS/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 KitWE mice carrying the Mb-scale deletion induced by the CRISPR/Cas9 system. As KitWE/WE embryos did not exhibit the abnormal phenotype, which was seen in KitWS/WS. We concluded that peri-implantation lethality in KitWS/WS was caused by a monogenic defect of Exoc1.

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