Peri-implantation lethality in mice carrying megabase-scale deletion on 5qc3.3 is caused by Exoc1 null mutation.
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.
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Seiya
S
Mizuno
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Kohei
K
Takami
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Yoko
Y
Daitoku
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Yoko
Y
Tanimoto
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Tra Thi Huong
TT
Dinh
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Saori
S
Mizuno-Iijima
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Yoshikazu
Y
Hasegawa
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Satoru
S
Takahashi
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Fumihiro
F
Sugiyama
Laborarory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Ken-ichi
K
Yagami
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D017353:Gene Deletion; D005804:Genes, Lethal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D017393:RNA Editing; D033921:Vesicular Transport Proteins
C000609696:Exoc1 protein, mouse; D033921:Vesicular Transport Proteins; D019009:Proto-Oncogene Proteins c-kit