Nantel F, Sassone-Corsi P
Institut de Genetique et de Biologie Moleculaire et Cellulaire, 1 rue Laurent Fries, BP 163, ILLKIRCH Cedex, C.U. de Strasbourg, France.
Front Biosci. 1996 Sep 1;1:d266-9. doi: 10.2741/a131.
Spermatogenesis is a complex differentiation process under the hormonal control of the hypothalamic-pituitary axis. The CREM gene encodes activators and repressors of cAMP-mediated gene transcription. The transcript corresponding to the activator isoform CREMtau is found at high levels in pachytene spermatocytes onwards. The CREMtau protein, however, is present only in post-meiotic spermatids where it activates the transcription of testis-specific genes, such as the protamines and transition proteins. Mice in which the CREM gene has been inactivated by homologous recombination have been generated. Homozygous male mutant mice are sterile and produce no spermatozoa. Histological analysis of the seminiferous tubules reveal a complete arrest of spermatogenesis at the first step of spermiogenesis. CREM deficiency results in the lack of post-meiotic gene expression and a ten-fold increase in apoptotic germ cells. These results demonstrate the essential role of CREM in spermatogenesis and are reminiscent of some cases of male infertility.
精子发生是一个在下丘脑 - 垂体轴激素控制下的复杂分化过程。CREM基因编码cAMP介导的基因转录的激活剂和抑制剂。对应于激活剂异构体CREMtau的转录本在粗线期精母细胞及之后的细胞中高水平存在。然而，CREMtau蛋白仅存在于减数分裂后的精子细胞中，在那里它激活睾丸特异性基因的转录，如鱼精蛋白和过渡蛋白。已经产生了通过同源重组使CREM基因失活的小鼠。纯合雄性突变小鼠不育，不产生精子。对生精小管的组织学分析显示精子发生在精子形成的第一步就完全停滞。CREM缺乏导致减数分裂后基因表达缺失，凋亡生殖细胞增加十倍。这些结果证明了CREM在精子发生中的重要作用，并让人联想到一些男性不育的病例。
