Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.
Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.
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DOI：
10.1111/pcmr.12030
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发表时间：
2013-01
影响因子：
4.3
通讯作者：
Hornyak TJ
中科院分区：
文献类型：
--
作者：
Ni C;Zhang D;Beyer LA;Halsey KE;Fukui H;Raphael Y;Dolan DF;Hornyak TJ
人类皮肤色素沉着综合征Waardenburg综合征2a型和Tietz综合征的特征是深度耳聋，但只有部分皮肤色素异常。这两种综合征都是由MITF突变引起的。为了阐明这些综合征中皮肤黑素细胞和耳黑素细胞之间的差异，研究了它们在杂合小眼白（MitfMi‐wh/+）小鼠中的发育和存活，并表征了这些小鼠的听力功能。MitfMi-wh/+小鼠具有严重的听力缺陷，其特征在于ABR阈值升高、畸变产物耳声发射减少、耳蜗内电位缺失、外毛细胞损失和血管纹异常。MitfMi-wh/+胚胎在胚胎发育期间比其野生型同窝仔具有更少的成黑素细胞。虽然耳蜗黑素细胞在出生时就存在，但它们在P1和P7之间从MitfMi-wh/+耳蜗消失。这些发现可能有助于深入了解黑素细胞和听力损失的机制，在人类色素沉着综合征，如Waardenburg综合征和Tietz综合征，并说明耳和滤泡黑素细胞之间的差异。
The human deafness-pigmentation syndromes Waardenburg syndrome type 2a and Tietz 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 Microphthalmia-White (MitfMi‐wh/+) mice were studied and hearing function of these mice characterized. MitfMi-wh/+ mice have a profound hearing deficit, characterized by elevated ABR thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. MitfMi-wh/+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the MitfMi-wh/+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as Waardenburg syndrome and Tietz syndrome, and illustrate differences between otic and follicular melanocytes.