{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have highlighted the critical role of DNAH9, a gene encoding an axonemal dynein heavy chain protein, in maintaining the proper structure and function of motile cilia. DNAH9 participates in the assembly and stabilization of outer dynein arms, which are essential for the generation of ciliary movement, thereby governing the left–right patterning process during embryonic development and ensuring normal cardiac function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn-depth analyses revealed that mutations in DNAH9 lead to decreased mRNA expression and aberrant protein products due to premature stop codons or exon skipping. These molecular defects result in ultrastructural abnormalities of the outer dynein arms, as observed via transmission electron microscopy. Functional studies using zebrafish and a Dnah9 knockout mouse model demonstrated that impaired DNAH9 function disrupts cardiac left–right patterning and compromises cardiac performance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, complementary research utilizing DNAH9 knockdown (KD) mouse models and airway organoids has recapitulated key clinical manifestations of primary ciliary dyskinesia, including reduced lung function, mucin accumulation, and increased immune cell infiltration. Detailed immunostaining, western blot, and co-immunoprecipitation assays further unveiled that DNAH9 interacts with other ciliary proteins such as CCDC114/GAS8, contributing to the stability of the ciliary apparatus. These models not only reinforce the pivotal role of DNAH9 in ciliary physiology but also serve as promising platforms for screening potential mitochondrial-targeted therapies aimed at restoring cilia beating."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Weicheng Chen, Yuan Zhang, Libing Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic DNAH9 mutations are identified in Chinese patients with defective left-right patterning and cilia-related complex congenital heart disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-021-02426-5"}], "href": "https://doi.org/10.1007/s00439-021-02426-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35050399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35050399"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rui Zheng, Wenhao Yang, Yuting Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-022-05010-5"}], "href": "https://doi.org/10.1038/s41419-022-05010-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35729109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35729109"}]}]}]}