| First Author | Wang C | Year | 2024 |
| Journal | Cell Mol Life Sci | Volume | 81 |
| Issue | 1 | Pages | 317 |
| PubMed ID | 39066891 | Mgi Jnum | J:354331 |
| Mgi Id | MGI:7731022 | Doi | 10.1007/s00018-024-05344-7 |
| Citation | Wang C, et al. (2024) ZMYND12 serves as an IDAd subunit that is essential for sperm motility in mice. Cell Mol Life Sci 81(1):317 |
| abstractText | Inner dynein arms (IDAs) are formed from a protein complex that is essential for appropriate flagellar bending and beating. IDA defects have previously been linked to the incidence of asthenozoospermia (AZS) and male infertility. The testes-enriched ZMYND12 protein is homologous with an IDA component identified in Chlamydomonas. ZMYND12 deficiency has previously been tied to infertility in males, yet the underlying mechanism remains uncertain. Here, a CRISPR/Cas9 approach was employed to generate Zmynd12 knockout (Zmynd12(-/-)) mice. These Zmynd12(-/-) mice exhibited significant male subfertility, reduced sperm motile velocity, and impaired capacitation. Through a combination of co-immunoprecipitation and mass spectrometry, ZMYND12 was found to interact with TTC29 and PRKACA. Decreases in the levels of PRKACA were evident in the sperm of these Zmynd12(-/-) mice, suggesting that this change may account for the observed drop in male fertility. Moreover, in a cohort of patients with AZS, one patient carrying a ZMYND12 variant was identified, expanding the known AZS-related variant spectrum. Together, these findings demonstrate that ZMYND12 is essential for flagellar beating, capacitation, and male fertility. |
