Effects of a Sertoli cell specific knockout of the connexin43-gene on the regulation of spermatogenesis in transgenis mice using the Cre/IoxP-recombination system

主要的睾丸间隙连接蛋白connexin43 （cx43）位于邻近的支持细胞（SC）之间以及SC和生殖细胞之间。它参与睾丸发育、生殖细胞分化、精子发生的起始和维持。由于cx43基因的完全破坏会导致围产期死亡，我们使用Cre/loxP重组系统在SC （SCCx43KO）中产生了一个条件cx43敲除（KO）小鼠，|在SC中缺乏cx43基因（SCCx43KO），以评估cx43在SC体内对精子发生的特异性功能。成年SCCx43KO~A小鼠睾丸下降和泌尿生殖道发育正常，但与杂合子和野生型（WT）仔鼠相比，|时睾丸大小和重量明显降低。组织学分析和生殖细胞特异性标记基因mRNA表达的定量分析显示，精原细胞数量显著减少，只有少数小管显示正常的精子发生。因此，sc特异性缺失的cx43居多。导致精子发生在精原细胞水平或仅SC综合征和小管内SC群集。我们的数据表明，cx43在SC中的表达是正常睾丸发育和精子发生的绝对需要。

The predominant testicular gap junctional protein connexin43 (cx43) is located « between neighboring Sertoli cells (SC) and between SC and germ cells. It is involved in • testicular development, germ cell differentiation, initiation and maintenance of spermatogenesis. As total disruption of the cx43 gene leads to perinatal death, we generated a « conditional cx43 knockout (KO) mouse using the Cre/loxP recombination system which | lacks the cx43 gene solely in SC (SCCx43KO) to evaluate the SC specific functions of cx43 on spermatogenesis in-vivo. Adult SCCx43KO~A mice showed normal testis descent and • development of the urogenital tract, but testis size and weight was drastically lower when | compared with heterozygous and wild-type (WT) littermates. Histological analysis and quantitation of mRNA expression of germ cell-specific marker genes revealed a significant , • reduction in the number of spermatogonia with only a few tubules left showing normal spermatogenesis. Thus, SC-specific deletion of cx43 mostly .resulted in an arrest of spermatogenesis at the level of spermatogonia or SC-only syndrome and to intratubular SC • clusters. Our data demonstrate that cx43 expression in SC is an absolute requirement for normal testicular development and spermatogenesis.