Mutations in the C1 element of the insulin promoter lead to diabetic phenotypes in homozygous mice

資料種別:

論文（リポジトリ）

責任表示:

Noguchi, Hirofumi ; Miyagi-Shiohira, Chika ; Nakashima, Yoshiki ; Kinjo, Takao ; Saitoh, Issei ; Watanabe, Masami

言語:

英語

出版情報:

Springer Nature, 2020-06-16

著者名:

Noguchi, Hirofumi

Miyagi-Shiohira, Chika

Nakashima, Yoshiki

Kinjo, Takao

Saitoh, Issei

Watanabe, Masami

続きを見る

掲載情報:

Communications Biology

ISSN:

2399-3642      

巻:

3

バージョン:

publisher

概要:

Genome editing technologies such as CRISPR–Cas9 are widely used to establish causal associations between mutations and phenotypes. However, CRISPR–Cas9 is rarely used to analyze promoter regions. The insulin promoter region (approximately 1,000 bp) directs β cell-specific expression of insulin, which in vitro studies show is regulated by ubiquitous, as well as pancreatic, β cell-specific transcription factors. However, we … are unaware of any confirmatory in vivo studies. Here, we used CRISPR–Cas9 technology to generate mice with mutations in the promoter regions of the insulin I (Ins1) and II (Ins2) genes. We generated 4 homozygous diabetic mice with 2 distinct mutations in the highly conserved C1 elements in each of the Ins1 and Ins2 promoters (3 deletions and 1 replacement in total). Remarkably, all mice with homozygous or heterozygous mutations in other loci were not diabetic. Thus, the C1 element in mice is required for Ins transcription in vivo. 続きを見る

URL:

http://hdl.handle.net/20.500.12000/47285