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

• Applicant: Professor Dr. Ralph Brehm
• Subject Area: Reproductive Medicine, Urology
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 34016037

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.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 181: Male Factor Infertility due to Impaired Spermatogenesis
• Participating Person: Professor Dr. Martin Bergmann