Investigation of a regulatory mechanism underlying androgen production in the fetal testis

MAMLD1 （Mastermind-like domain containing 1）被认为是导致人类尿道下裂的基因。在交配后12.5 ~ 18.5 d，野生型雄性小鼠胎睾丸中Mamld1 mRNA的表达逐渐稳定升高。为了研究MAMLD1在小鼠中的作用，我们制造了MAMLD1敲除小鼠。Mamld1基因敲除雄性小鼠显示出轻度但显著降低胎睾丸间质细胞专有基因（Star、Cyp11a1、Cyp17a1和Hsd3b1）的mRNA水平。这些结果提供了MAMLD1在雄激素产生中起作用的证据，表明存在小鼠和人类共有的机制。进一步的研究将探索mamld1依赖性分子网络在类固醇激素产生和mamld1突变患者病理状况中的作用。

MAMLD1 (Mastermind-like domain containing 1) has been identified as a gene responsible for with hypospadias in humans. The Mamld1 mRNA expression was gradually and steadily increased from 12.5 to 18.5 day post coitum in the fetal testis of wild-type male mice. To study the role of MAMLD1 in mice, we produced Mamld1 knockout mice. Mamld1 knockout male mice showed mildly but significantly reduced fetal testicular mRNA levels of genes exclusively expressed in Leydig cells (Star, Cyp11a1, Cyp17a1, and Hsd3b1). These results provide the evidence that MAMLD1 plays a role in androgen production, indicating the presence of a mechanism shared between mouse and human. Further studies will explore the MAMLD1-dependent molecular network in the steroid hormone production and the pathological condition of MAMLD1-mutated patients.