Type 2 diabetes-like hyperglycemia in a backcross model of NZO and SJL mice: characterization of a susceptibility locus on chromosome 4 and its relation with obesity

Type 2 diabetes-like hyperglycemia in a backcross model of NZO and SJL mice: characterization of a susceptibility locus on chromosome 4 and its relation with obesity. L Plum , R Kluge , K Giesen , J Altmüller , J R Ortlepp and H G Joost Institute of Pharmacology and Toxicology, Medical Faculty of the Technical University Aachen, Germany. Abstract A backcross model of New Zealand obese mice (NZO) with the lean, atherosclerosis-resistant SJL strain was established to locate genes responsible for obesity, insulin resistance, and type 2 diabetes-like hyperglycemia. In male NZO x F1 backcross mice, a major susceptibility locus for the development of hyperglycemia and hypoinsulinemia (Nidd/SJL) was identified on chromosome 4 between the markers D4Mit278 and D4Mit232, 10-28 cM distal of the previously described Nidd1 locus. The diabetogenic allele has presumably been contributed by the SJL genome, and it appeared to be responsible for approximately 60% of the total prevalence of hyperglycemia. The presence of Nidd/SJL did not alter body weight or weight gain by week 12. Thereafter, it was associated with reduced weight gain or weight loss, presumably as a consequence of decompensated hyperglycemia. In all male backcross mice, the prevalence of hyperglycemia at week 22 increased with the body weight at week 12, suggesting that the development of hyperglycemia was dependent on the degree of obesity. In the absence of Nidd/SJL, mice weighing