Matsumoto Takahiro, Kawano Hirotaka, Shiina Hiroko, Sato Takashi, Kato Shigeaki
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, and.
ERATO, Japan Science and Technology, Kawaguchi, Saitama, Japan.
Reprod Med Biol. 2007 Feb 16;6(1):11-17. doi: 10.1111/j.1447-0578.2007.00159.x. eCollection 2007 Mar.
The androgen receptor (AR) is a ligand-dependent transcription factor involved in the regulation of many different physiological processes. Dysfunction of AR causes diverse clinical conditions, such as testicular feminization mutation (Tfm) syndrome and prostate cancer. However, the molecular basis of the AR in these disorders largely remains unknown, as a result of a lack of genetic models. Using conditional targeting technique with Cre-loxP system, we successfully generated null AR mutant (ARKO) mice. The ARKO males grew healthily, but they showed typical Tfm abnormalities. The ARKO males exhibited late onset of obesity with impaired bone metabolism and sexual behaviors. No overt abnormality was found in female ARKO mice, but a premature ovarian failure-like phenotype was found with impaired folliculogenesis. Thus, andorogen/AR system supports normal reproduction as well as normal female reproduction. (Reprod Med Biol 2007; : 11-17).
雄激素受体(AR)是一种依赖配体的转录因子,参与多种不同生理过程的调控。AR功能障碍会导致多种临床病症,如睾丸女性化突变(Tfm)综合征和前列腺癌。然而,由于缺乏遗传模型,AR在这些疾病中的分子基础很大程度上仍不清楚。利用Cre-loxP系统的条件性靶向技术,我们成功培育出了雄激素受体基因敲除(ARKO)小鼠。ARKO雄性小鼠生长健康,但表现出典型的Tfm异常。ARKO雄性小鼠出现肥胖发病延迟,伴有骨代谢和性行为受损。雌性ARKO小鼠未发现明显异常,但发现有卵泡发生受损的类似卵巢早衰的表型。因此,雄激素/AR系统支持正常的生殖以及正常的雌性生殖。(《生殖医学与生物学》2007年;:11 - 17)