DNAH2, also known as Dynein Axonemal Heavy Chain 2, is crucial for sperm flagella formation and functions in the homologous recombination repair pathway. It is associated with multiple morphological abnormalities of the sperm flagella (MMAF) and Fanconi anemia (FA) [1,2,3,4]. Genetic models, like gene-knockout mouse models, are valuable for studying its functions.

In mouse models, Dnah2-null males are infertile. Dnah2-null sperm cells show absent, short, bent, coiled, and/or irregular flagella, consistent with the MMAF phenotype. The ultrastructure of flagella is severely disorganized, and the absence of DNAH2 compromises the expression of other axonemal components. In U2OS cells, down-regulation of DNAH2 increases cell sensitivity to DNA inter-strand crosslinks, reduces FANCD2 protein enrichment at DNA damage sites, and influences FANCD2 ubiquitination modification [1,3].

In conclusion, DNAH2 is essential for sperm flagella formation and plays a role in the homologous recombination repair pathway. Studies using gene-knockout mouse models have revealed its significance in male infertility related to MMAF and in the pathogenesis of Fanconi anemia.

References:

1. Chang, Lixian, Gao, Xingjie, Wang, Yuxia, Yuan, Weiping, Zhu, Xiaofan. 2021. DNAH2 facilitates the homologous recombination repair of Fanconi anemia pathway through modulating FANCD2 ubiquitination. In Blood science (Baltimore, Md.), 3, 71-77. doi:10.1097/BS9.0000000000000076. https://pubmed.ncbi.nlm.nih.gov/35402838/

2. Li, Yang, Sha, Yanwei, Wang, Xiong, Tang, Yunge, Lu, Zhongxian. 2019. DNAH2 is a novel candidate gene associated with multiple morphological abnormalities of the sperm flagella. In Clinical genetics, 95, 590-600. doi:10.1111/cge.13525. https://pubmed.ncbi.nlm.nih.gov/30811583/

3. Hwang, Jae Yeon, Nawaz, Shoaib, Choi, Jungmin, Ahmad, Wasim, Chung, Jean-Ju. 2021. Genetic Defects in DNAH2 Underlie Male Infertility With Multiple Morphological Abnormalities of the Sperm Flagella in Humans and Mice. In Frontiers in cell and developmental biology, 9, 662903. doi:10.3389/fcell.2021.662903. https://pubmed.ncbi.nlm.nih.gov/33968937/

4. Gao, Yang, Tian, Shixiong, Sha, Yanwei, Zhang, Feng, He, Xiaojin. 2021. Novel bi-allelic variants in DNAH2 cause severe asthenoteratozoospermia with multiple morphological abnormalities of the flagella. In Reproductive biomedicine online, 42, 963-972. doi:10.1016/j.rbmo.2021.01.011. https://pubmed.ncbi.nlm.nih.gov/33771466/