Faculty Research 1990 - 1999


NIDDM genes in mice: deleterious synergism by both parental genomes contributes to diabetogenic thresholds.

Document Type


Publication Date



Animal, Chrmosome Mapping, Diabetes Mellitus, Non-Insulin-Dependent, Differential Susceptibility, Genome Glucose Intolerance/genetics/physiopathology, Male, Mice, Obesity/genetics, Phenotype

JAX Source

Diabetes 1998 Aug;47(8):1287-95


RR08911/RR/NCRR, CA34196/CA/NCI


We used mouse genetics to model how polygenic thresholds for the transition from impaired glucose tolerance (IGT) to NIDDM are reached. NON/Lt and NZO/Hl are inbred mouse strains selected for IGT and polygenic obesity, respectively. Their F1 male progeny consistently developed NIDDM. Genetic analysis of F2 males from both cross directions identified an NON-derived diabetogenic locus, Nidd 1, on chromosome (Chr) 4 near the leptin receptor. This locus was associated with reduced plasma insulin, increased non-fasted blood glucose, and lower body weight. Another NON-derived diabetogenic locus on Chr 18 (Nidd2) that controls blood glucose was identified. An NZO-derived diabetogenic region on Chr 11 (Nidd3), possibly comprising two separate loci, reduced ability to sustain elevated plasma insulin and significantly reduced weight gain over time. Thus, the diabetogenic synergism between genetic loci from strains separately exhibiting subthreshold defects perturbing glucose homeostasis underscores the likely complexity of the inheritance of obesity-associated forms of NIDDM in humans.

Please contact the Joan Staats Library for information regarding this document.