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 diabetes mellitus. Fetuses in this strain present anomalies of the viscera, and the incidence increases in fetuses from dams with clinically manifested diabetes. To examine the role of maternal diabetes and the genetical influence in inducing heterotaxy, NOD dams were mated with males of the ICR strain (the original strain of the NOD) and with C57BL/6J sires (not genetically related to the NOD). The frequency of visceroatrial 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 heterotaxy showed a tendency toward right isomerism of the viscera and had severe cardiac defects, such as endocardial cushion defect and double-outlet right ventricle or transposition of the great arteries. The fetal 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 fetal growth. These findings demonstrate that the liability to heterotaxy induced by maternal diabetes is influenced by the fetal genotype.
Morishima
M
M
Research Division, Heart Institute of Japan, Tokyo Women's Medical College, Japan.
Yasui
H
H
Ando
M
M
Nakazawa
M
M
Takao
A
A
D000015:Abnormalities, Multiple / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001835:Body Weight; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D016640:Diabetes, Gestational; D005314:Embryonic and Fetal Development; D005260:Female; D006330:Heart Defects, Congenital / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D009024:Morphogenesis; D011247:Pregnancy; D012857:Situs Inversus / Q000209:etiology*; D014781:Viscera / Q000002:abnormalities*