Department of Otorhinolaryngology Head and Neck Surgery, Xijing Hospital, Airforce Military Medical University, Xi'an, China.
Department of Otorhinolaryngology Head and Neck Surgery, Xijing Hospital, Airforce Military Medical University, Xi'an, China.
Biochem Biophys Res Commun. 2022 Dec 3;632:69-75. doi: 10.1016/j.bbrc.2022.09.081. Epub 2022 Sep 24.
Autosomal recessive nonsyndromic auditory neuropathy is attributed to a genetic etiology. We identified a compound heterozygous missense variant, c.G736A (p.G246S) and c.C2954T (p.T985 M) in TNN of affected patients in a pedigree via candidate gene screening and exome sequencing. To determine the genetic etiology of deafness in the pedigree with a heterozygous missense variant in the gene TNN encoding tenascin-W associated with autosomal recessive nonsyndromic auditory neuropathy, the cochlear expression of tenascin-W was evaluated at mRNA and protein levels in mice, and Tnn knock out mice were generated and utilized to study the function of Tnn in the auditory system. Immunofluorescence stainings showed that tenascin-W was mainly expressed in the somatic cytoplasm of spiral ganglion neurons of mice. Homozygous Tnn knockout was lethal in mice, whereas Tnn heterozygous mice showed decreases in spiral ganglion neuron density and progressive hearing loss. We demonstrate that tenascin-W is expressed in the murine cochleae and is essential for the development of spiral ganglion neurons. An abnormal expression of tenascin-W can influence the development and function of SGNs and affect the function of the auditory system.
常染色体隐性非综合征性听神经病归因于遗传病因。我们通过候选基因筛查和外显子组测序，在一个家系中发现了患有该病的患者 TNN 中的复合杂合错义变异 c.G736A（p.G246S）和 c.C2954T（p.T985M）。为了确定与常染色体隐性非综合征性听神经病相关的基因 TNN 中的杂合错义变体编码 tenascin-W 的耳聋家系的遗传病因，在小鼠中评估了 tenascin-W 的基因表达，在 mRNA 和蛋白水平上评估了 tenascin-W 的基因表达，并生成了 Tnn 敲除小鼠，用于研究 Tnn 在听觉系统中的功能。免疫荧光染色显示 tenascin-W 主要表达在小鼠螺旋神经节神经元的体细胞细胞质中。Tnn 纯合子敲除在小鼠中是致命的，而 Tnn 杂合子小鼠表现出螺旋神经节神经元密度降低和进行性听力损失。我们证明 tenascin-W 在小鼠耳蜗中表达，对于螺旋神经节神经元的发育是必需的。tenascin-W 的异常表达会影响 SGN 的发育和功能，并影响听觉系统的功能。
