| First Author | Sakano D | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 12187 |
| PubMed ID | 32699230 | Mgi Jnum | J:294041 |
| Mgi Id | MGI:6453053 | Doi | 10.1038/s41598-020-68987-z |
| Citation | Sakano D, et al. (2020) Insulin2(Q104del) (Kuma) mutant mice develop diabetes with dominant inheritance. Sci Rep 10(1):12187 |
| abstractText | 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. |
