Trpm5-KO Mouse

Trpm5, a Ca(2+)-activated cation channel, is crucial in chemosensory signaling. It is the final component in a cascade triggered by the activation of G protein-coupled receptors in taste cells responding to bitter, sweet, or umami molecules, relying on the enzyme PLCβ2 [1,3]. Beyond taste cells, it is expressed in chemosensory cells throughout the digestive, respiratory, and olfactory systems, as well as in pancreatic islets, contributing to insulin secretion [1]. Genetic models, like knockout mice, are valuable for studying its function.

Trpm5 -/- mice lack type II taste perception and show reduced glucose-induced insulin secretion, highlighting its role in taste transduction and pancreatic β-cell function [2]. In high-fat-diet-fed mice, TRPM5 expression in pancreatic islets decreases, and in vitro, lipotoxicity reduces TRPM5 expression in pancreatic β-cells, leading to β-cell dysfunction, suggesting its importance in diabetes-related pancreatic β-cell health [4]. LPS-stimulated B cells from Trpm5-deficient mice have increased cytosolic calcium, enhanced proliferation, and more inflammatory cytokine production, demonstrating its role in regulating B-cell responses [5].

In conclusion, Trpm5 is essential for taste transduction and insulin secretion. Through gene knockout mouse models, its role in diabetes-related pancreatic β-cell function and B-cell regulation in the context of immune responses has been revealed. These findings contribute to understanding the underlying mechanisms of taste-related and metabolic diseases, as well as immune-related conditions.

References:

1. Liman, Emily R. . TRPM5. In Handbook of experimental pharmacology, 222, 489-502. doi:10.1007/978-3-642-54215-2_19. https://pubmed.ncbi.nlm.nih.gov/24756718/

2. Vennekens, R, Mesuere, M, Philippaert, K. 2017. TRPM5 in the battle against diabetes and obesity. In Acta physiologica (Oxford, England), 222, . doi:10.1111/apha.12949. https://pubmed.ncbi.nlm.nih.gov/28834354/

3. Liman, E R. . TRPM5 and taste transduction. In Handbook of experimental pharmacology, , 287-98. doi:. https://pubmed.ncbi.nlm.nih.gov/17217064/

4. Wang, Kai-Yuan, Wu, Shi-Mei, Yao, Zheng-Jian, Zhu, Yun-Xia, Han, Xiao. 2024. Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreatic β-cell Dysfunction. In Current medical science, 44, 346-354. doi:10.1007/s11596-023-2795-5. https://pubmed.ncbi.nlm.nih.gov/38517672/

5. Sakaguchi, Taiki, Okumura, Ryu, Ono, Chisato, Baba, Yoshihiro, Takeda, Kiyoshi. . TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes. In Cell reports, 31, 107755. doi:10.1016/j.celrep.2020.107755. https://pubmed.ncbi.nlm.nih.gov/32521253/