Disruption of the autism-related gene Pak1 causes stereocilia disorganization,hair cell loss,and deafness in mice

• 作者: Cheng Cheng Yilin Hou Zhonghong Zhang Yanfei Wang Ling Lu Liyan Zhang Pei Jiang Song Gao Qiaojun Fang Chengwen Zhu Junyan Gao Xufeng Liu Wei Xie Zhengping Jia Zhigang Xu Xia Gao Renjie Chai
• 来源期刊: 遗传学报
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Original Research
• 页码范围: 324-332
• 页数: 9页
• 语种: 英文

摘要

Several clinical studies have reported that hearing loss is correlated with autism in children.However,little is known about the underlying mechanism between hearing loss and autism.p21-activated kinases (PAKs)are a family of serine/threonine kinases that can be activated by multiple signaling molecules,particularly the Rho family of small GTPases.Previous studies have shown that Pak1 mutations are associated with autism.In the present study,we take advantage of Pak1 knockout (Pak1-/-) mice to investigate the role of PAK1 in hearing function.We find that PAK1 is highly expressed in the postnatal mouse cochlea and that PAK1 deficiency leads to hair cell (HC) apoptosis and severe hearing loss.Further investigation indicates that PAK1 deficiency downregulates the phosphorylation of cofilin and ezrin-radixin-moesin and the expression of βll-spectrin,which further decreases the HC synapse density in the basal turn of cochlea and disorganized the HC stereocilia in all three turns of cochlea in Pak1 /-mice.Overall,our work demonstrates that the autism-related gene Pak1 plays a crucial role in hearing function.As the first candidate gene linking autism and hearing loss,Pak1 may serve as a potential target for the clinical diagnosis of autism-related hearing loss.