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- Title
Insulin2Q104del (Kuma) mutant mice develop diabetes with dominant inheritance.
- Authors
Sakano, Daisuke; Inoue, Airi; Enomoto, Takayuki; Imasaka, Mai; Okada, Seiji; Yokota, Mutsumi; Koike, Masato; Araki, Kimi; Kume, Shoen
- Abstract
Insulin gene mutations have been identified to cause monogenic diabetes, and most of which developed permanent neonatal diabetes at young ages before 6 months of age in humans. To establish an animal model of permanent diabetes, we performed genome editing using the CRISPR/Cas9 system. We generated a novel Kuma mutant mice with p.Q104del in the Insulin2 (Ins2) gene in a BRJ background that exhibits a severe immune deficiency. Kuma mutant mice are non-obese and developed hyperglycemia from 3 weeks after birth in both males and females, which are inherited in a dominant mode. Kuma mutant mice displayed reduced insulin protein levels from 3-weeks-old, which seem to be caused by the low stability of the mutant insulin protein. Kuma mutant showed a reduction in islet size and islet mass. Electron microscopic analysis revealed a marked decrease in the number and size of insulin granules in the beta-cells of the mutant mice. Hyperglycemia of the mutant can be rescued by insulin administration. Our results present a novel insulin mutation that causes permanent early-onset diabetes, which provides a model useful for islet transplantation studies.
- Subjects
INSULIN; DIABETES; HYPERGLYCEMIA; ELECTRON microscopic diagnosis; PANCREATIC beta cells
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-68987-z