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

Scientific Reports
Seiya MizunoKen-ichi Yagami

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.

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Citations

May 6, 2016·Frontiers in Cell and Developmental Biology·Magdalena Martin-UrdirozIsabelle Jourdain
Jul 3, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hisayo Nishida-Fukuda
Feb 28, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Michael E CoulterChristopher A Walsh
Apr 8, 2016·Experimental Animals·Yoshikazu HasegawaFumihiro Sugiyama
Sep 27, 2016·Journal of Cellular Physiology·Toshiaki TanakaMitsuyoshi Iino
Jun 8, 2017·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Michelle N Knowlton, Cynthia L Smith
Mar 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Xiaoyu ZhuYing Gu
Apr 26, 2020·Methods : a Companion to Methods in Enzymology·Saori Mizuno-IijimaFumihiro Sugiyama
Aug 15, 2021·Mammalian Genome : Official Journal of the International Mammalian Genome Society·M N Perry, C L Smith

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Methods Mentioned

BETA
PCR

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