Mice homozygous for this TRPM8 targeted mutation are viable and fertile, with no differences in core body temperature compared to wildtype. Functional TRPM8 transcripts are absent in trigeminal ganglia from homozygous mutants however,a truncated, non-functional transcript is generated. Immunostaining of trigeminal ganglia, corneal afferents, and spinal cord dorsal horn reveals loss of TRPM8 expression in homozygous mutants. TRPM8-deficient mice exhibit behavioral deficits in their ability to discriminate between cold and warm surfaces, or to respond to evaporative cooling. Homozygous mice are not completely cold insensitive as they avoid contact with surfaces below 10 C (albeit with reduced efficiency). Cultured sensory neurons and intact sensory nerve fibers from TRPM8-deficient mice exhibit profoundly diminished responses to cold. These TRMP8 (transient receptor potential cation channel, subfamily M, member 8 (also called TRP melastatin 8 or cold and menthol receptor 1 (CMR1))) mutant mice may be useful for neurological studies including thermosensation over a wide range of cold temperatures, detection of cold thermal stimuli by primary afferent sensory neurons, nociceptive processing, and pain response behavior.
