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Title :Mutations in the C1 element of the insulin promoter lead to diabetic phenotypes in homozygous mice
Authors :Noguchi, Hirofumi
Miyagi-Shiohira, Chika
Nakashima, Yoshiki
Kinjo, Takao
Saitoh, Issei
Watanabe, Masami
Issue Date :16-Jun-2020
Abstract :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.
URL :https://doi.org/10.1038/s42003-020-1040-z
Type Local :雑誌掲載論文
ISSN :2399-3642
Publisher :Springer Nature
URI :http://hdl.handle.net/20.500.12000/47285
Citation :Communications Biology Vol.3
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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