Dnai1-KO Mouse

Dnai1, or dynein axonemal intermediate chain 1, is a key structural element of the ciliary outer dynein arm (ODA). It is crucial for normal ciliary activity and the subsequent clearance of mucus from the conducting airways in humans [2]. Mutations in DNAI1 can lead to primary ciliary dyskinesia (PCD), an autosomal recessive disorder [2].

In research, DNAI1 mutations were found in 2%-10% of PCD patients in different studies [1,4]. For example, in one cohort of 104 unrelated PCD patients, mutations on both alleles of gene DNAI1 were identified in only 2% [1]. In another study of 179 families with PCD, 10% of patients were estimated to harbor DNAI1 mutations, with most occurring as a common founder IVS1+2_3insT or in exons 13, 16, and 17 [4]. A PCD pig model with a disrupted DNAI1 gene was developed using CRISPR-Cas9. The PCD pig airway cilia lacked the outer dynein arm, had impaired beating, and mucociliary transport was impaired. Neonatal PCD pigs developed neonatal respiratory distress, and older ones had worsening airway mucus obstruction, inflammation, and bacterial infection, closely mimicking the human PCD disease phenotype [3].

In conclusion, DNAI1 is essential for normal ciliary function and mucus clearance in the airways. The study of DNAI1-related gene knockout models, such as the PCD pig model, helps to understand the pathophysiology of PCD and potentially develop effective treatments for this debilitating respiratory disease.