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

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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Article number309
JournalCommunications Biology
Issue number1
Publication statusPublished - Dec 1 2020

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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