Teramoto S, Hatakenaka N, Shirasu Y
Mitsukaida Laboratories, Institute of Environmental Toxicology, Ibaraki, Japan.
Teratology. 1991 Jul;44(1):101-6. doi: 10.1002/tera.1420440114.
Effects of the Ay gene, a coat color gene, on susceptibility to hydrocortisone fetotoxicity and teratogenicity were investigated by using the congenic strain of C57BL/6-Ay (Ay/a) which had been maintained by repeated back-crosses of the Ay gene to the C57BL/6 (a/a) background. Matings were conducted as follows (female x male): group I, a/a; group II, a/a x Ay/a; and group III, Ay/a x a/a. Pregnant females were subcutaneously given daily doses of 0, 12.5, 25, or 50 mg/kg of hydrocortisone on days 10-13 of pregnancy. On day 18 of pregnancy, fetuses were sexed, weighed, and examined for external abnormalities. In group I, the mean fetal weight was significantly decreased at a dose of 25 mg/kg or more. The incidences of cleft palate were 3.2 and 22.7% at 25 and 50 mg/kg, respectively. In group II, in which half of the fetuses were expected to carry the Ay gene, the mean fetal weight was decreased significantly at 12.5 mg/kg or more. The incidence of cleft palate in group II at 50 mg/kg was 44.2%, which was significantly higher than that in group I. In group III, in which maternal mice as well as half of their fetuses carried the Ay gene, a decrease in the mean fetal weight was greater than in group II. In addition, the mean percentage of fetal resorptions was significantly increased at 50 mg/kg. The incidence of cleft palate in group III was significantly increased at 25 mg/kg (10.5%) when compared with those in groups I and II. These results indicate that the Ay gene may be associated with susceptibility to hydrocortisone fetotoxicity and teratogenicity in mice.
通过使用将Ay基因反复回交到C57BL/6(a/a)背景上所培育的C57BL/6-Ay(Ay/a)同基因品系,研究了毛色基因Ay对氢化可的松胎儿毒性和致畸性易感性的影响。交配方式如下(雌性×雄性):第一组,a/a;第二组,a/a×Ay/a;第三组,Ay/a×a/a。在妊娠第10 - 13天,给怀孕雌性小鼠皮下每日注射0、12.5、25或50mg/kg的氢化可的松。在妊娠第18天,对胎儿进行性别鉴定、称重,并检查外部异常情况。在第一组中,剂量为25mg/kg及以上时,平均胎儿体重显著降低。在25mg/kg和50mg/kg时,腭裂发生率分别为3.2%和22.7%。在第二组中,预计有一半胎儿携带Ay基因,剂量为12.5mg/kg及以上时,平均胎儿体重显著降低。第二组在50mg/kg时的腭裂发生率为44.2%,显著高于第一组。在第三组中,母鼠及其一半胎儿携带Ay基因,平均胎儿体重的降低幅度大于第二组。此外,在50mg/kg时,胎儿吸收的平均百分比显著增加。与第一组和第二组相比,第三组在25mg/kg时的腭裂发生率显著增加(10.5%)。这些结果表明,Ay基因可能与小鼠对氢化可的松胎儿毒性和致畸性的易感性有关。