Tmem132e-KO Mouse

TMEM132E, encoding transmembrane protein 132E, has been implicated in multiple biological processes. It is highly expressed in inner hair cells and may be involved in the function of α9α10 nicotinic acetylcholine receptors in hair cells, as transmembrane inner ear (TMIE) or TMEM132e can act as an auxiliary subunit for ion channel function [4]. It may also be related to metabolic diseases as it was identified as a potential candidate gene through a computational approach integrating various data in a mouse model of obesity and diabetes [5].

Mutations in TMEM132E have been linked to autosomal-recessive nonsyndromic hearing impairment (ARNSHI). Compound heterozygous variants in TMEM132E were observed in affected members of a Pakistani-origin family with prelingual profound sensorineural hearing impairment, strengthening the evidence of its involvement in ARNSHI [2]. In a Chinese family, a homozygous missense mutation in TMEM132E was identified as the causative variant for autosomal-recessive nonsyndromic hearing loss DFNB99, and knockdown of the tmem132e ortholog in zebrafish affected hair cell mechanotransduction [3]. Additionally, in triple-negative breast cancer, TMEM132E ablation suppresses tumor progression and restores tamoxifen sensitivity by inducing ERα expression [1].

In conclusion, TMEM132E plays crucial roles in inner hair cell-related functions and is associated with autosomal-recessive nonsyndromic hearing impairment. Its potential roles in metabolic diseases and cancer also highlight its significance in understanding disease mechanisms. The study of TMEM132E through genetic models such as gene knockdown in zebrafish and gene ablation in cancer cells helps in revealing its functions in specific biological processes and disease conditions.

References:

1. Gao, Shang, Sun, Ping, Wang, Zekun, Li, Jiangxia, Liu, Qiji. 2024. TMEM132E ablation suppresses tumor progression and restores tamoxifen sensitivity by inducing ERα expression in triple-negative breast cancer. In Genes & diseases, 12, 101396. doi:10.1016/j.gendis.2024.101396. https://pubmed.ncbi.nlm.nih.gov/39584071/

2. Liaqat, Khurram, Hussain, Shabir, Bilal, Muhammad, Ahmad, Wasim, Leal, Suzanne M. 2019. Further evidence of involvement of TMEM132E in autosomal recessive nonsyndromic hearing impairment. In Journal of human genetics, 65, 187-192. doi:10.1038/s10038-019-0691-4. https://pubmed.ncbi.nlm.nih.gov/31656313/

3. Li, Jiangxia, Zhao, Xiaohan, Xin, Qian, Gong, Yaoqin, Liu, Qiji. 2014. Whole-exome sequencing identifies a variant in TMEM132E causing autosomal-recessive nonsyndromic hearing loss DFNB99. In Human mutation, 36, 98-105. doi:10.1002/humu.22712. https://pubmed.ncbi.nlm.nih.gov/25331638/

4. Gu, Shenyan, Knowland, Daniel, Matta, Jose A, Kweon, Hae-Jin, Bredt, David S. 2020. Hair cell α9α10 nicotinic acetylcholine receptor functional expression regulated by ligand binding and deafness gene products. In Proceedings of the National Academy of Sciences of the United States of America, 117, 24534-24544. doi:10.1073/pnas.2013762117. https://pubmed.ncbi.nlm.nih.gov/32929005/

5. Gottmann, Pascal, Ouni, Meriem, Zellner, Lisa, Walther, Dirk, Schürmann, Annette. 2020. Polymorphisms in miRNA binding sites involved in metabolic diseases in mice and humans. In Scientific reports, 10, 7202. doi:10.1038/s41598-020-64326-4. https://pubmed.ncbi.nlm.nih.gov/32350386/