Hearing dysfunction in heterozygous M itf Mi‐wh /+ mice, a model for W aardenburg syndrome type 2 and T ietz syndrome

Summary The human deafness‐pigmentation syndromes, Waardenburg syndrome ( WS ) type 2a, and T ietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF . To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous M icrophthalmia‐ W hite ( M itf Mi‐wh /+) mice were studied and hearing function of these mice characterized. M itf Mi‐wh /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. M itf Mi‐wh /+ embryos have fewer melanoblasts during embryonic development than their wild‐type littermates. Although cochlear melanocytes are present at birth, they disappear from the M itf Mi‐wh /+ cochlea between P 1 and P 7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness‐pigmentation syndromes such as WS and T ietz syndrome and illustrate differences between otic and follicular melanocytes.