Dnah2-KO Mouse

DNAH2, short for Dynein Axonemal Heavy Chain 2, is crucial for normal biological functions related to DNA repair and sperm flagella formation. In the context of DNA repair, it is associated with the homologous recombination repair pathway of Fanconi anemia (FA), a genetic disease [1]. In sperm, it is essential for the proper development and function of the flagella, being linked to sperm motility [2,3,4]. Genetic models, such as gene knockout mouse models, are valuable tools to study DNAH2's functions.

In gene-targeted mouse models, Dnah2-null males are infertile, with sperm cells showing multiple morphological abnormalities of the flagella (MMAF), including absent, short, bent, coiled, or irregular flagella [3]. The flagella ultrastructure is severely disorganized, and the absence of DNAH2 compromises the expression of other axonemal components like DNAH1 and RSPH3, suggesting its importance in multiple steps of sperm flagella formation [3]. In cell lines, down-regulation of DNAH2 in MMC-treated U2OS cells increases sensitivity to DNA inter-strand crosslinks, reduces FANCD2 enrichment at DNA damage sites, and influences FANCD2 ubiquitination modification, indicating its role in the FA homologous recombination repair pathway [1].

In conclusion, DNAH2 is essential for sperm flagella formation and plays a role in the homologous recombination repair pathway of FA. The use of Dnah2 knockout mouse models has significantly contributed to understanding its role in male infertility associated with MMAF and the pathogenesis of FA.