| First Author | Noguchi H | Year | 2020 |
| Journal | Commun Biol | Volume | 3 |
| Issue | 1 | Pages | 309 |
| PubMed ID | 32546815 | Mgi Jnum | J:293751 |
| Mgi Id | MGI:6453673 | Doi | 10.1038/s42003-020-1040-z |
| Citation | Noguchi H, et al. (2020) Mutations in the C1 element of the insulin promoter lead to diabetic phenotypes in homozygous mice. Commun Biol 3(1):309 |
| abstractText | 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 beta cell-specific expression of insulin, which in vitro studies show is regulated by ubiquitous, as well as pancreatic, beta 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. |
