The pathogenesis of congenital lipoid adrenal hyperplasia in gonads revealed by StAR knockout mice

StAR基因敲除小鼠揭示先天性性腺类脂性肾上腺增生症的发病机制

• 批准号: 13670838
• 负责人: HASEGAWA Tomonobu
• 金额: $ 2.56万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670838/
• 关键词: StAE; StAR knockout mice; StAR; GnRH double knockout mice; testes; ovary; lipid deposit; ゴナドトロピン; エストラジオール; 卵胞成熟; テストステロン; 精子形成

I generated steroidogenic acute regulatory protein (StAR) knockout mice (StAR KO) using gene targeting. I crossed StAR KO mice and naturally occurred gonadotropin-releasiug hormone (GnRH) gene abnormal mice to generate StAR/GnRH double mutant mice (StAR/GnRH double KO). I investigated gonadal histology in StAR KO and StAR/GnRH double KO from birth to 8 weeks.1. at birth : (1) Testes in StAR KO had mild lipid deposits in interstitial space. Ovaries did not. (2) Both testes and ovaries in StAR/GnRH double KO did not have any Iipid deposits.2. from birth to 6 weeks : (1) Both testes and ovaries in StAR KO did not have massive lipid deposits. (2) Both testes and ovaries in StAR/GnRH double KO did not have any lipid deposits.3. 8 weeks : (1) Both testes and ovaries in StAR/GnRH double KO were hypoplastic compared to StAR KO. (2) Both testes and ovaries in StAR KO had massive lipid deposits. (3) Both testes and ovaries in StAR/GnRH double KO lacked lipid deposits. (4) Exogenous gonadotoropin treatment in StAR/GnRH double KO induced lipid deposits in both testes and ovaries.These data strongly indicated that lipid deposits in StAR KO gonads after pubertal age is gonadotoropin dependent.

我利用基因靶向技术培育出了类固醇生成急性调节蛋白 (StAR) 基因敲除小鼠 (StAR KO)。我将StAR KO小鼠与天然发生促性腺激素释放激素（GnRH）基因异常的小鼠杂交，产生StAR/GnRH双突变小鼠（StAR/GnRH双KO）。我研究了StAR KO和StAR/GnRH双KO从出生到8周的性腺组织学。1．出生时：（1）StAR KO 的睾丸间质内有轻度脂质沉积。卵巢没有。 (2)StAR/GnRH双KO的睾丸和卵巢均未出现脂质沉积。2．从出生到6周：（1）StAR KO的睾丸和卵巢均没有大量脂质沉积。 (2)StAR/GnRH双KO的睾丸和卵巢均未出现脂质沉积。3． 8周：(1)与StAR KO相比，StAR/GnRH双KO中的睾丸和卵巢均发育不全。 (2)StAR KO的睾丸和卵巢均存在大量脂质沉积。 (3)StAR/GnRH双KO的睾丸和卵巢均缺乏脂质沉积。 (4)StAR/GnRH双KO中的外源性促性腺激素治疗诱导睾丸和卵巢中的脂质沉积。这些数据强烈表明青春期后StAR KO性腺中的脂质沉积是促性腺激素依赖性的。

项目成果

Caron KM, Hasegawa T, et al.: "Animal model of impaired steroidogenesis"Harwood Academic Publishers, U.S.A(in press).

Caron KM、Hasekawa T 等人：“类固醇生成受损的动物模型”Harwood 学术出版社，美国（出版中）。

Caron KM, Hasegawa T, et al.: "Animal model of impaired steroidogenesis"Harwood Academic Publication, U.S.A. (in press).

Caron KM、Hasekawa T 等人：“类固醇生成受损的动物模型”Harwood 学术出版社，美国（出版中）。

Caron KM, Hasegawa T, et al.: "Animal model of impaired steroidogenesis"Harwood Academic Publication. (in press).

Caron KM、Hasekawa T 等人：“类固醇生成受损的动物模型”Harwood 学术出版物。