| First Author | Austin ALF | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 12 | Pages | 2667-2677 |
| PubMed ID | 32994272 | Mgi Jnum | J:300475 |
| Mgi Id | MGI:6502777 | Doi | 10.2337/db20-0570 |
| Citation | Austin ALF, et al. (2020) The KINGS Ins2 (+/G32S) Mouse: A Novel Model of beta-Cell Endoplasmic Reticulum Stress and Human Diabetes. Diabetes 69(12):2667-2677 |
| abstractText | Animal models are important tools in diabetes research because ethical and logistical constraints limit access to human tissue. beta-Cell dysfunction is a common contributor to the pathogenesis of most types of diabetes. Spontaneous hyperglycemia was developed in a colony of C57BL/6J mice at King's College London (KCL). Sequencing identified a mutation in the Ins2 gene, causing a glycine-to-serine substitution at position 32 on the B chain of the preproinsulin 2 molecule. Mice with the Ins2 (+/G32S) mutation were named KCL Ins2 G32S (KINGS) mice. The same mutation in humans (rs80356664) causes dominantly inherited neonatal diabetes. Mice were characterized, and beta-cell function was investigated. Male mice became overtly diabetic at approximately 5 weeks of age, whereas female mice had only slightly elevated nonfasting glycemia. Islets showed decreased insulin content and impaired glucose-induced insulin secretion, which was more severe in males. Transmission electron microscopy and studies of gene and protein expression showed beta-cell endoplasmic reticulum (ER) stress in both sexes. Despite this, beta-cell numbers were only slightly reduced in older animals. In conclusion, the KINGS mouse is a novel model of a human form of diabetes that may be useful to study beta-cell responses to ER stress. |
