INFLUENCE OF GENETIC AND MATERNAL DIABETES IN THE PATHOGENESIS OF VISCEROATRIAL HETEROTAXY IN MICE

The NOD mouse is known as a spontaneous model of insulin-dependent dia betes mellitus. Fetuses in this strain present anomalies of the viscer a, and the incidence increases in fetuses from dams with clinically ma nifested diabetes. To examine the role of maternal diabetes and the ge netical influence in inducing heterotaxy, NOD dams were mated with mal es of the ICR strain (the original strain of the NOD) and with C57BL/6 J sires (not genetically related to the NOD). The frequency of viscero atrial heterotaxy in fetuses from diabetic dams varied with the fetal genotype, being 65% (33/51) in NODxNOD (dam x sire, respectively), 24% (12/50) in NODxICR, and 7% (4/57) in NODxC57BL/6J. The cases with het erotaxy showed a tendency toward right isomerism of the viscera and ha d severe cardiac defects, such as endocardial cushion defect and doubl e-outlet right ventricle or transposition of the great arteries. The f etal body weight from diabetic dams in each mating was lower than that from non-diabetic dams (P < 0.05), suggesting that maternal diabetes, rather than abnormal situs, is the main determinant for decreased fet al growth. These findings demonstrate that the liability to heterotaxy induced by maternal diabetes is influenced by the fetal genotype. (C) 1997 Wiley-Liss, Inc.