Cortisone-induced cleft palate in the brachymorphic mouse.
Previous studies have shown that the autosomal recessive gene brachymorphic (bm/bm), which is maintained on a C57BL/6J (C57) background, reduces limb growth and sulfation of cartilage proteoglycans. Hydrocortisone administered on gestational days 11-14 resulted in 20% CP in the C57 mouse, but 95% CP in the bm/bm mouse. The bm/bm mouse had a median effective dose for CP of 45 mg/kg, compared to 325 mg/kg for C57 and 40 mg/kg for A/J. Morphometric analysis indicated that the time of palatal elevation was delayed in the bm/bm relative to the C57 mouse both with and without hydrocortisone treatment. The amount of cytoplasmic glucocorticoid receptor protein present in the bm/bm palate on day 14 was the same as the amount found in the C57 palate, and was not elevated as it is in the A/J palate. The levels of cyclic AMP in the bm/bm palate on day 14 were 30-70% higher than that found in the C57 palate with or without hydrocortisone. These results suggest that both bm/bm and A/J exhibit a delay in palatal shelf rotation and elevated levels of cyclic AMP, which appear to be predisposing factors for cortisone-induced cleft palate. These strains differ in that elevated levels of steroid receptors are present in A/J palate, whereas lower levels are found in the C57 and bm/bm mice.
D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced*; D003348:Cortisone / Q000633:toxicity*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006854:Hydrocortisone / Q000633:toxicity; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013045:Species Specificity
D011965:Receptors, Glucocorticoid; D000242:Cyclic AMP; D003348:Cortisone; D006854:Hydrocortisone