RRC ID 35938
Author Mizuno S, Takami K, Daitoku Y, Tanimoto Y, Dinh TT, Mizuno-Iijima S, Hasegawa Y, Takahashi S, Sugiyama F, Yagami K.
Title Peri-implantation lethality in mice carrying megabase-scale deletion on 5qc3.3 is caused by Exoc1 null mutation.
Journal Sci Rep
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.
Volume 5
Pages 13632
Published 2015-9-8
DOI 10.1038/srep13632
PII srep13632
PMID 26346620
PMC PMC4562154
MeSH 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
IF 3.998
Times Cited 10
DNA material px330-PK (RDB13939) px330-NE (RDB13940) pCAG-EGxxFP-PK (RDB13941) pCAG-EGxxFP-NE (RDB13942).