Tmc7-KO Mouse

Tmc7, a member of the transmembrane channel-like (TMC) protein family, has diverse functions. It has been implicated in processes such as mechanotransduction, acrosome biogenesis during spermatogenesis, and may be involved in cancer-related events like pancreatic cancer metastasis [1-4]. In the context of mechanotransduction, it functions as a suppressor of Piezo2 in primary sensory neurons, influencing peripheral mechanotransduction [1,5]. In spermatogenesis, it is essential for acrosome biogenesis, and its deficiency leads to male infertility phenotypes similar to human oligo-astheno-teratozoospermia [2,3].

Genetic deletion of Tmc7 in primary sensory ganglia neurons in vivo enhances physiological and pathological mechanosensory transduction, increasing the proportion of rapidly adapting currents conducted by Piezo2 in dorsal root ganglion neurons and accelerating their deactivation kinetics [1]. In mice, Tmc7-/-mice show abnormal sperm head, disorganized mitochondrial sheaths, and reduced elongating spermatids, due to aberrant Golgi morphology and impaired fusion of Golgi-derived vesicles to the developing acrosome [2]. Also, deletion of Tmc7 in male mice causes abnormal swelling of trans-Golgi network vesicles in elongated spermatids [3]. In pancreatic cancer, alternative splicing events of Tmc7 are associated with liver metastasis, and knockdown of exon 17 of Tmc7 inhibits pancreatic cancer cell proliferation, invasion, and migration [4].

In conclusion, Tmc7 is crucial for normal mechanotransduction in sensory neurons and acrosome biogenesis in spermatogenesis. The gene knockout mouse models have revealed its significant role in these processes, as well as its potential involvement in pancreatic cancer progression. Understanding Tmc7 provides insights into the underlying mechanisms of these biological processes and disease conditions, potentially guiding future research in related areas [1-4].

References:

1. Zhang, Xiaoxue, Shao, Jichen, Wang, Caixue, Zhang, Hailin, Du, Xiaona. 2024. TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction. In Cell reports, 43, 114014. doi:10.1016/j.celrep.2024.114014. https://pubmed.ncbi.nlm.nih.gov/38568807/

2. Wang, Jing, Yin, Yingying, Yang, Lei, Liu, Hongbin, Liu, Zhaojian. 2024. TMC7 deficiency causes acrosome biogenesis defects and male infertility in mice. In eLife, 13, . doi:10.7554/eLife.95888. https://pubmed.ncbi.nlm.nih.gov/39269275/

3. Lv, Zheng, Sun, Longjie, Chen, Xuexue, Shao, Yujing, Liu, Jiali. 2024. TMC7 is required for spermiogenesis and male fertility by regulating TGN-derived vesicles. In International journal of biological macromolecules, 293, 139070. doi:10.1016/j.ijbiomac.2024.139070. https://pubmed.ncbi.nlm.nih.gov/39732242/

4. Weng, Yuanchi, Qian, Hao, Hong, Liwen, Deng, Xiaxing, Shen, Baiyong. 2023. Identification of EMT-related alternative splicing event of TMC7 to promote invasion and migration of pancreatic cancer. In Frontiers in immunology, 13, 1089008. doi:10.3389/fimmu.2022.1089008. https://pubmed.ncbi.nlm.nih.gov/36713450/

5. West, Aaron Keith, Schneider, Eve Rebecca. 2024. A novel suppressor of Piezo2 in rodent nociceptors. In Trends in neurosciences, 47, 478-479. doi:10.1016/j.tins.2024.05.003. https://pubmed.ncbi.nlm.nih.gov/38762363/