Dnah17-KO Mouse

DNAH17, dynein axonemal heavy chain 17, is crucial for spermatogenesis and male fertility [2,3,4]. It is specifically expressed in testes and localized to sperm flagella [4]. Dysfunction in DNAH17 can lead to sperm flagellum defects, which are associated with asthenozoospermia and male infertility [1,3,4].

Knockout Dnah17 rats generated by CRISPR/Cas9 gene editing showed that homozygous male rats were infertile, with significantly decreased sperm count and increased apoptosis in testes, suggesting that DNAH17 is essential for spermatogenesis in male rats [2]. In humans, various DNAH17 mutations have been identified in patients with multiple morphological abnormalities of the sperm flagella (MMAF) phenotype, which is a severe form of asthenozoospermia. These patients generally have worse pregnancy outcomes following intracytoplasmic sperm injection (ICSI), but ICSI combined with assisted oocyte activation (AOA) may improve the outcome of assisted reproductive techniques for men with DNAH17 variants [1].

In conclusion, DNAH17 is essential for spermatogenesis and male fertility. Studies on knockout rat models and human patients with DNAH17 mutations have revealed its crucial role in sperm development and the implications for male infertility. These findings provide important insights for understanding the genetic basis of male infertility and for improving assisted reproductive techniques [1,2].

References:

1. Song, Bing, Yang, Tianjin, Shen, Qunshan, Cao, Yunxia, He, Xiaojin. 2023. Novel mutations in DNAH17 cause sperm flagellum defects and their influence on ICSI outcome. In Journal of assisted reproduction and genetics, 40, 2485-2492. doi:10.1007/s10815-023-02897-7. https://pubmed.ncbi.nlm.nih.gov/37574497/

2. Chen, Liling, Ouyang, Jiamin, Li, Xueqing, Liao, Yuandongs, Zhang, Qingjiong. . DNAH17 is essential for rat spermatogenesis and fertility. In Journal of genetics, 100, . doi:. https://pubmed.ncbi.nlm.nih.gov/33764336/

3. Sha, Yanwei, Wei, Xiaoli, Ding, Lu, Zhang, Yi, Ji, Zhiyong. 2019. DNAH17 is associated with asthenozoospermia and multiple morphological abnormalities of sperm flagella. In Annals of human genetics, 84, 271-279. doi:10.1111/ahg.12369. https://pubmed.ncbi.nlm.nih.gov/31841227/

4. Zhang, Beibei, Ma, Hui, Khan, Teka, Zhang, Yuanwei, Shi, Qinghua. . A DNAH17 missense variant causes flagella destabilization and asthenozoospermia. In The Journal of experimental medicine, 217, . doi:10.1084/jem.20182365. https://pubmed.ncbi.nlm.nih.gov/31658987/