| First Author | Sarkar PS | Year | 2004 |
| Journal | Hum Mol Genet | Volume | 13 |
| Issue | 14 | Pages | 1421-31 |
| PubMed ID | 15163633 | Mgi Jnum | J:91207 |
| Mgi Id | MGI:3046123 | Doi | 10.1093/hmg/ddh161 |
| Citation | Sarkar PS, et al. (2004) Six5 is required for spermatogenic cell survival and spermiogenesis. Hum Mol Genet 13(14):1421-31 |
| abstractText | Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia, Leydig cell hyperproliferation and increased follicle stimulating hormone (FSH) levels. DM1 results from a CTG expansion that causes transcriptional silencing of the flanking SIX5 allele. Loss of Six5 results in male sterility and a progressive decrease in testicular mass with age. We demonstrate a strict requirement of Six5 for both spermatogenic cell survival and spermiogenesis. Leydig cell hyperproliferation and increased intra-testicular testosterone levels are observed in the Six5-/- mice. Although increased FSH levels are observed in the Six5+/- and Six5-/- mice, serum testosterone levels and intra-testicular inhibin alpha and inhibin beta B levels are not altered in the Six5 mutant animals when compared with controls. Significantly, steady-state c-Kit levels are reduced in the Six5-/- testis. Thus, decreased c-Kit levels could contribute to the elevated spermatogenic cell apoptosis and Leydig cell hyperproliferation in the Six5-/- mice. The results support the hypothesis that the reduced SIX5 levels contribute to the male reproductive defects in DM1. |
