Dcdc2a-KO Mouse

Dcdc2a, a member of the doublecortin domain-containing protein superfamily, likely plays a role in microtubule formation and stabilization, which is crucial for normal cellular functions related to cilia. It may be involved in pathways related to the development and function of inner ear cells [1].

A point mutation in Dcdc2a causes non-syndromic recessive deafness DFNB66 in a Tunisian family. In the rat inner ear, Dcdc2a localizes to the kinocilia of sensory hair cells and the primary cilia of non-sensory supporting cells. Overexpression in non-polarized COS7 cells induces long microtubule-based cytosolic cables. In hair and supporting cells, the deafness mutant Dcdc2a causes cilium structural defects and length ratio increases. In zebrafish, the ortholog dcdc2b is essential for hair cell development, survival, and function [1].

In conclusion, Dcdc2a is a key gene in regulating the length of hair cell kinocilia and supporting cell primary cilia, likely through its role in microtubule formation and stabilization. The findings from these genetic models, including zebrafish, help to understand its role in the context of deafness, revealing its importance in inner ear cell function and the development of this sensory deficit [1].

References:

1. Grati, M'hamed, Chakchouk, Imen, Ma, Qi, Liu, Xue Zhong, Masmoudi, Saber. 2015. A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation. In Human molecular genetics, 24, 2482-91. doi:10.1093/hmg/ddv009. https://pubmed.ncbi.nlm.nih.gov/25601850/