Genetic differences among the A/J X C57BL/6J recombinant inbred mouse lines and their degree of association with glucocorticoid-induced cleft palate.
Hydrocortisone sodium phosphate was injected intramuscularly into A/J, C57BL/6J and recombinant inbred lines from these two parental lines to study the genetics of steroid-induced cleft palate in a situation of identical maternal and fetal genotypes. The strains were typed for H-2 (the major histocompatibility locus), beta-glucuronidase and beta 2-microglobulin, which served as markers on chromosomes 17, 5 and 2, respectively. Hepatic glucocorticoid binding capacity had been previously measured in Hepes buffer and Hepes buffer plus dithiothreitol (DTT). The level of glucocorticoid binding in Hepes buffer and in Hepes plus DTT, as well as their ratio, was compared to the incidence of steroid-induced cleft palate in the recombinant inbred lines. A correlation was found between the response of glucocorticoid binding to DTT (expressed as a ratio of binding in the presence of DTT to binding without DTT) and hydrocortisone-induced cleft palate. When analyzing the effect of the three chromosomal markers on hydrocortisone-induced cleft palate, the b alleles of beta 2-microglobulin and of beta-glucuronidase were associated with a higher incidence. Genetic analyses of the differences between these two inbred strains of mice in the incidence of steroid-induced cleft palate show it not to be monogenic.
D000483:Alleles; D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D005966:Glucuronidase / Q000235:genetics; D006854:Hydrocortisone; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013045:Species Specificity; D001613:beta 2-Microglobulin / Q000235:genetics
D011965:Receptors, Glucocorticoid; D001613:beta 2-Microglobulin; D005966:Glucuronidase; D006854:Hydrocortisone