Dnai2-flox Mouse

DNAI2, also known as dynein axonemal intermediate chain 2, is a gene crucial for cilia and flagella movement as it is a component of the outer dynein arm (ODA) complexes in motile cilia. It is involved in biological processes like cilium movement and is associated with pathways relevant to ciliary function [1,2].

Mutations in DNAI2 have been found to cause primary ciliary dyskinesia (PCD). In a study, homozygous loss-of-function DNAI2 mutations in humans led to ODA defects, as seen by lack of DNAI2 protein expression and absence of ODA heavy chains DNAH5 and DNAH9 from ciliary axonemes [2]. In another study, a novel founder variant in DNAI2 was identified in consanguineous families with PCD, and TEM analysis showed lack of ODAs [3]. A newborn with PCD was found to have a novel 6.9 kb microdeletion in DNAI2, suggesting it as a causative factor for PCD and potentially a new genetic risk factor for normal pressure hydrocephalus (NPH) [4]. In a medaka fish PCD mutant, disruption of dnai2 led to reduced outer dynein arms in cilia and LR defects [5].

In conclusion, DNAI2 is essential for the proper assembly and function of the outer dynein arms in motile cilia. Studies on DNAI2 mutations in human and animal models have revealed its crucial role in PCD, highlighting its significance in understanding the molecular mechanisms underlying this disorder.