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

Sci Rep. 2015 Sep 8:5:13632. doi: 10.1038/srep13632.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Chromosome Deletion*
  • Chromosome Mapping
  • Crosses, Genetic
  • Gene Deletion*
  • Genes, Lethal*
  • Male
  • Mice
  • Mice, Knockout
  • Mutation
  • Phenotype*
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-kit / genetics
  • RNA Editing
  • Vesicular Transport Proteins

Substances

  • Exoc1 protein, mouse
  • Vesicular Transport Proteins
  • Proto-Oncogene Proteins c-kit