Dnah9, a core component of outer dynein arms in cilia and flagellum, is crucial for ciliary function. Cilia play essential roles in multiple biological processes, and the outer dynein arms are vital for ciliary beat generation. Dysfunction of Dnah9-related ciliary function can impact various physiological functions and is associated with ciliopathies [3,4,5].

In animal models, Dnah9 knockdown (KD) in mice recapitulated phenotypes of patients with primary ciliary dyskinesia (PCD), such as low lung function, mucin accumulation, and increased immune cell infiltration. Immunostaining and other analyses showed that DNAH9 interacted with CCDC114/GAS8 and affected their protein levels. Also, Dnah9 KD airway organoids mimicked PCD phenotypes and were used to screen drugs that could partially elevate cilia beating [1]. In zebrafish, dnah9 knockdown led to disturbed cardiac left-right patterning without affecting ciliogenesis in Kupffer's vesicle (KV). And Dnah9 knockout (KO) C57BL/6n mice had compromised cardiac function [2].

In summary, Dnah9 is essential for proper ciliary function, which is crucial for multiple physiological processes. Studies using Dnah9 KD and KO mouse models, as well as zebrafish knockdown models, have significantly enhanced our understanding of how Dnah9 dysfunction contributes to diseases like PCD, cardiac abnormalities, and cilia-related complex congenital heart disease. These models also offer potential platforms for drug screening and further research on ciliopathies [1,2].

References:

1. Zheng, Rui, Yang, Wenhao, Wen, Yuting, Xu, Wenming, Liu, Hanmin. 2022. Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening. In Cell death & disease, 13, 559. doi:10.1038/s41419-022-05010-5. https://pubmed.ncbi.nlm.nih.gov/35729109/

2. Chen, Weicheng, Zhang, Yuan, Shen, Libing, Zhao, Jianyuan, Zhou, Xiangyu. 2022. Biallelic DNAH9 mutations are identified in Chinese patients with defective left-right patterning and cilia-related complex congenital heart disease. In Human genetics, 141, 1339-1353. doi:10.1007/s00439-021-02426-5. https://pubmed.ncbi.nlm.nih.gov/35050399/

3. Tang, Dongdong, Sha, Yanwei, Gao, Yang, He, Xiaojin, Cao, Yunxia. 2021. Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia. In Reproductive biology and endocrinology : RB&E, 19, 27. doi:10.1186/s12958-021-00709-0. https://pubmed.ncbi.nlm.nih.gov/33610189/

4. Loges, Niki T, Antony, Dinu, Maver, Ales, Omran, Heymut, Schmidts, Miriam. 2018. Recessive DNAH9 Loss-of-Function Mutations Cause Laterality Defects and Subtle Respiratory Ciliary-Beating Defects. In American journal of human genetics, 103, 995-1008. doi:10.1016/j.ajhg.2018.10.020. https://pubmed.ncbi.nlm.nih.gov/30471718/

5. Yan, Fei, Zhi, Weiwei, Wei, Yazhen, Xu, Wenming, Zheng, Rui. 2024. Novel variants in DNAH9 are present in two infertile patients with severe asthenospermia. In Journal of human genetics, 70, 105-111. doi:10.1038/s10038-024-01304-y. https://pubmed.ncbi.nlm.nih.gov/39523437/