| First Author | Fujiwara Y | Year | 2023 |
| Journal | Reproduction | Volume | 166 |
| Issue | 6 | Pages | 437-450 |
| PubMed ID | 37801077 | Mgi Jnum | J:342545 |
| Mgi Id | MGI:7548932 | Doi | 10.1530/REP-23-0166 |
| Citation | Fujiwara Y, et al. (2023) New allele of mouse DNA/RNA helicase senataxin causes meiotic arrest and infertility. Reproduction 166(6):437-450 |
| abstractText | IN BRIEF: A new allele of the senataxin gene Setxspcar3 causes meiotic arrest of spermatocytes with aberrant DNA damage and accumulation of R-loops. ABSTRACT: An unbiased screen for discovering novel mouse genes for fertility identified the spcar3, spermatocyte arrest 3, mutant phenotype. The spcar3 mutation identified a new allele of the Setx gene, encoding senataxin, a DNA/RNA helicase that regulates transcription termination by resolving DNA/RNA hybrid R-loop structures. The Setxspcar3 mutant mice exhibit male infertility and female subfertility. Histology of the Setxspcar3 mutant testes revealed the absence of spermatids and mature spermatozoa in the seminiferous tubules. Cytological analysis of chromosome preparations of the Setxspcar3 mutant spermatocytes revealed normal synapsis, but aberrant DNA damage in the autosomes, defective formation of the sex body, and arrest of meiosis in mid-prophase. Additionally, Setxspcar3 testicular cells exhibit abnormal accumulation of R-loops. Transient expression assays identified regions of the senataxin protein required for sub-nuclear localization. Together, these results not only confirm that senataxin is required for normal meiosis and spermatogenesis but also provide a new resource for the determination of its role in maintaining R-loop formation and genome integrity. |
