Trpm5-KO Mouse

Trpm5, a Ca(2+)-activated cation channel, is crucial in taste and other chemosensory signaling [1,2,4]. In taste cells, it's the final element in a cascade triggered by the activation of G protein-coupled receptors for bitter, sweet, or umami tastes, relying on PLCβ2 to break down PIP2 and release Ca(2+) to activate Trpm5 [1,4]. It's distributed in chemosensory cells across the digestive, respiratory, and olfactory systems, and in pancreatic islets, contributing to insulin secretion [1]. Genetic models, like knockout mice, are valuable for studying its functions.

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 mice, TRPM5 expression in pancreatic islets decreases, and in vitro studies with palmitate show lipotoxicity inhibits TRPM5 expression in pancreatic β-cells, driving β-cell dysfunction [5]. In B cells, Trpm5-deficient mice exhibit enhanced calcium-dependent responses to lipopolysaccharide, leading to increased proliferation and cytokine production, and exacerbation of endotoxic shock [6].

In conclusion, Trpm5 is essential for taste transduction and insulin secretion. Gene knockout mouse models have revealed its role in taste perception, pancreatic β-cell function, and immune responses such as in B cells during lipopolysaccharide stimulation. Understanding Trpm5 functions through these models may provide insights into diseases related to taste disorders, diabetes, and immune dysregulation.

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. Uchida, Kunitoshi. 2024. TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels. In The journal of physiological sciences : JPS, 74, 43. doi:10.1186/s12576-024-00937-0. https://pubmed.ncbi.nlm.nih.gov/39294615/

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

5. 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/

6. 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/