Temperature sensing shapes behavior and cellular functions, yet the molecular basis of thermosensitivity in non-neuronal cells remains poorly defined. Microglia are resident immune cells of the central nervous system that help maintain brain homeostasis via immune surveillance and injury responses. We previously showed that microglial motility is temperature dependent and is largely mediated by the thermosensitive ion channel transient receptor potential vanilloid 4 (TRPV4), a thermosensitive ion channel. However, the contribution of transient receptor potential melastatin 4 (TRPM4) is unclear because suitable Trpm4 mutant mice were not available in our earlier work. Here, we generated functional Trpm4-knockout mice (TRPM4KO) using CRISPR/Cas9 genome editing based on a published strategy. Time-lapse imaging of primary microglia across a range of temperatures revealed that Trpm4 deficiency did not alter temperature-dependent motility in vitro. These results indicate that TRPM4 is dispensable for temperature-dependent microglial motility.
Nishimoto et al. (2026) studied this question.