2024-03-29T07:47:45Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02011250
2023-08-03T05:43:20Z
1642838163960:1642838338003
1642838403551:1642838407795
Mutations in the C1 element of the insulin promoter lead to diabetic phenotypes in homozygous mice
Noguchi, Hirofumi
Miyagi-Shiohira, Chika
Nakashima, Yoshiki
Kinjo, Takao
Saitoh, Issei
Watanabe, Masami
open access
Creative Commons Attribution 4.0
https://creativecommons.org/licenses/by/4.0/
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.
論文
Springer Nature
2020-06-16
eng
journal article
VoR
http://hdl.handle.net/20.500.12000/47285
http://hdl.handle.net/20.500.12000/47285
https://u-ryukyu.repo.nii.ac.jp/records/2011250
https://doi.org/10.1038/s42003-020-1040-z
https://doi.org/10.1038/s42003-020-1040-z
2399-3642
Communications Biology
3
https://u-ryukyu.repo.nii.ac.jp/record/2011250/files/s42003-020-1040-z.pdf