Analyses of congenital lipoid adrenal hyperplasia and nuerodteroids using StAR knockout mice

1)建立了载脂蛋白A-1(Apo A1)和类固醇生成调节蛋白(STAP)双基因敲除小鼠(Double KO)。我们用油红O染色对野生、STAR基因敲除(STAR KO)和双重KO的类固醇合成组织进行了组织学分析。结果(1)新生儿肾上腺和睾丸脂肪沉积呈星形，呈双KO&GT；卵巢内未见脂类沉积，各基因型均未见。(2)幼体(8周龄)精巢和卵巢的脂肪沉积呈星形，呈KO&GT；这些结果提示循环中的胆固醇在STAR缺乏所致的脂质堆积中起主导作用。2)用免疫组织化学方法研究了STAR和胆固醇侧链裂解酶(P450soc)在脑内的蛋白表达。在运动皮质和下丘脑，我们发现了一些同时表达STAR和P450soc的细胞。这些数据支持了STAR在脑内神经类固醇合成中的功能意义。

1)We generated Apolipoprotein A-1(Apo A1) and steroidogenic regulatory protein(StAP) double knockout mice (double KO). We analyzed histology of steroidogenic tissues in wild, StAR knockout(StAR KO), and double KO using oil red O staining. Results (1)In neonates, lipid deposit in adrenal gland and testis showed StAR KO>>double KO>wild. No lipid deposit in ovary was observed in any genotypes. (2)In young adult (8 week old), lipid deposit in testis and ovary showed StAR KO>>double KO>wild. These data suggested the predominant role of circulating cholesterol in the lipid accumulation by StAR deficiency.2)We investigated the protein expression of StAR and cholesterol side chain cleavage enzyme(P450soc) in brain using immunohistochemical staining. In motor cortex as well as hyppocampus, we identidied some cells expressing both StAR and P450soc. These data supported the functional significance of StAR in neurosteroidogenesis in brain.