| First Author | Brüning JC | Year | 1997 |
| Journal | Cell | Volume | 88 |
| Issue | 4 | Pages | 561-72 |
| PubMed ID | 9038347 | Mgi Jnum | J:38502 |
| Mgi Id | MGI:85885 | Doi | 10.1016/s0092-8674(00)81896-6 |
| Citation | Bruning JC, et al. (1997) Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell 88(4):561-72 |
| abstractText | NIDDM is a polygenic disease characterized by insulin resistance in muscle, fat, and liver, followed by a failure of pancreatic beta cells to adequately compensate for this resistance despite increased insulin secretion. Mice double heterozygous for null alleles in the insulin receptor and insulin receptor substrate-1 genes exhibit the expected approximately 50% reduction in expression of these two proteins, but a synergism at a level of insulin resistance with 5- to 50-fold elevated plasma insulin levels and comparable levels of beta cell hyperplasia. At 4-6 months of age, 40% of these double heterozygotes become overtly diabetic. This NIDDM mouse model in which diabetes arises in an age-dependent manner from the interaction between two genetically determined, subclinical defects in the insulin signaling cascade demonstrates the role of epistatic interactions in the pathogenesis of common diseases with non-Mendelian genetics. |
