Hearing impairment in SMS1 deficient mice SMS1欠損マウスにおける難聴
Hearing impairment in SMS1 deficient mice
Sphingomyelin (SM), a major species of sphingolipids, is a ubiquitous component ofcell membranes and plays vital roles in signal transduction and cell growth and survival.However, its physiological functions have not been fully elucidated. Here we haveexamined the role of SM synthesis mediated by SM synthase (SMS) family members,SMS1 and SMS2, in auditory function. Hearing ability of SMS1 null mice, assessedwith an association learning experiment and with auditory brainstem response, wasimpaired, especially at low frequency range; the impairment was accompanied byabnormalities of stria vascularis (SV), i.e., a decrease in the width of SV and adisorganization of marginal cells. Further, fluorescent immunostaining and westernblotting revealed an altered expression pattern and reduced level of KCNQ1 channels inmarginal cells. In addition, SMS1 knockout (KO) mice exhibited a significant decreaseof endocochlear potential and distortion product otoacoustic emissions, suggesting thedefects of cochlear functions. And observation of more macrophage invasion into SV atapical region than other regions may explain the low frequency hearing loss in theseSMS1 KO mice. Mice lacking SMS2, however, showed no detectable hearing loss.Taken together, our results suggest hearing impairment in SMS1 deficient mice but notin SMS2 deficient mice. Defects in SV may at least in part account for the hearingimpairment in SMS1 deficient mice.