Department of Pediatrics, Washington University, St. Louis, MO 63110, USA.
Mol Cell Endocrinol. 2011 Feb 10;333(1):85-95. doi: 10.1016/j.mce.2010.12.019. Epub 2010 Dec 21.
Transcription factor GATA4 is expressed in Sertoli and Leydig cells and is required for proper development of the murine fetal testis. The role of GATA4 in adult testicular function, however, has remained unclear due to prenatal lethality of mice harboring homozygous mutations in Gata4. To characterize the function of GATA4 in the adult testis, we generated mice in which Gata4 was conditionally deleted in Sertoli cells using Cre-LoxP recombination with Amhr2-Cre. Conditional knockout (cKO) mice developed age-dependent testicular atrophy and loss of fertility, which coincided with decreases in the quantity and motility of sperm. Histological analysis demonstrated Sertoli cell vacuolation, impaired spermatogenesis, and increased permeability of the blood-testis barrier. RT-PCR analysis of cKO testes showed decreased expression of germ cell markers and increased expression of testicular injury markers. Our findings support the premise that GATA4 is a key transcriptional regulator of Sertoli cell function in adult mice.
转录因子 GATA4 表达于 Sertoli 和 Leydig 细胞中，对于小鼠胚胎睾丸的正常发育是必需的。然而，由于 Gata4 基因纯合突变的小鼠存在胚胎致死性，GATA4 在成年睾丸功能中的作用仍不清楚。为了研究 GATA4 在成年睾丸中的功能，我们利用 Amhr2-Cre 进行 Cre-LoxP 重组，在 Sertoli 细胞中条件性敲除 Gata4，从而构建了 Gata4 条件性敲除（cKO）小鼠。cKO 小鼠表现出年龄依赖性的睾丸萎缩和生育能力丧失，这与精子数量和活力的下降相一致。组织学分析显示 Sertoli 细胞空泡化、精子发生受损以及血睾屏障通透性增加。对 cKO 睾丸的 RT-PCR 分析显示，生殖细胞标志物的表达降低，睾丸损伤标志物的表达增加。我们的研究结果支持这样一个前提，即 GATA4 是成年小鼠 Sertoli 细胞功能的关键转录调节因子。
