| First Author | Morohoshi A | Year | 2019 |
| Journal | Dev Biol | Volume | 445 |
| Issue | 2 | Pages | 178-188 |
| PubMed ID | 30391586 | Mgi Jnum | J:270079 |
| Mgi Id | MGI:6274597 | Doi | 10.1016/j.ydbio.2018.10.023 |
| Citation | Morohoshi A, et al. (2019) The ubiquitin ligase subunit beta-TrCP in Sertoli cells is essential for spermatogenesis in mice. Dev Biol 445(2):178-188 |
| abstractText | beta-TrCP is the substrate recognition subunit of an SCF-type ubiquitin ligase. We recently showed that deletion of the genes for both beta-TrCP1 and beta-TrCP2 paralogs in germ cells of male mice resulted in accumulation of the transcription factor DMRT1 and spermatogenic failure, whereas systemic beta-TrCP1 knockout combined with beta-TrCP2 knockdown had previously been shown to lead to disruption of testicular organization and accumulation of the transcription factor SNAIL. Here we investigated beta-TrCP function in Sertoli cells by generating mice with targeted deletion of the beta-TrCP2 gene in Sertoli cells on a background of whole-body beta-TrCP1 knockout. Loss of beta-TrCP in Sertoli cells caused infertility due to a reduction in the number of mature sperm. Whereas spermatogonia were not affected, male germ cells entered meiosis prematurely and the number of round spermatids was reduced in the mutant mice. Extracts of Sertoli cells and of the testis from the mutant mice manifested accumulation of SNAIL, and expression of the SNAIL target gene for E-cadherin was down-regulated in Sertoli cells from these animals. Our results indicate that beta-TrCP in Sertoli cells regulates Sertoli cell-germ cell interaction through degradation of SNAIL, with such regulation being critical for sperm development. |
