A Novel ENU-Induced Mutation in Myo6 Causes Vestibular Dysfunction and Deafness.
A Novel ENU-Induced Mutation in Myo6 Causes Vestibular Dysfunction and Deafness.
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一种新的 ENU 诱导的 Myo6 突变导致前庭功能障碍和耳聋
DOI：
10.1371/journal.pone.0154984
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Xu PX
中科院分区：
文献类型：
--
作者：
Wong EY;Xu CY;Brahmachary M;Xu PX
小鼠N-乙基-N-亚硝基脲（ENU）诱变已经产生了许多有用的人类疾病动物模型。在这里，我们描述了一种新的ENU诱导的小鼠突变株特纳（Tur），显示盘旋和摇头行为和进行性听力损失的鉴定。Tur/Tur纯合子动物缺乏Preyer反射和翻正反射，并显示严重的甩头和伸手反应缺陷。我们将Tur突变定位到9号染色体上11 cM的关键区域，其中包括肌球蛋白VI。直接序列分析揭示了Myo 6基因外显子8中的c.820A>T取代，其将运动域中的氨基酸Asn 200改变为Ile（p.N200I）。内耳毛细胞的免疫组织化学，扫描电镜和组织学分析显示内耳毛细胞变性和结构畸形的静纤毛在特纳纯合子突变小鼠的耳蜗。我们的数据表明，这种新的小鼠品系提供了一个有用的模型，为未来的研究肌球蛋白VI在哺乳动物的听觉和非听觉系统和人类综合征的功能。
Mouse N-ethyl-N-nitrosourea (ENU) mutagenesis has generated many useful animal models for human diseases. Here we describe the identification of a novel ENU-induced mouse mutant strain Turner (Tur) that displays circling and headtossing behavior and progressive hearing loss. Tur/Tur homozygous animals lack Preyer and righting reflexes and display severe headtossing and reaching response defect. We mapped the Tur mutation to a critical region of 11 cM on chromosome 9 that includes myosin VI. Direct sequence analysis revealed a c.820A>T substitution in exon 8 of the Myo6 gene that changes amino acid Asn200 to Ile (p.N200I) in the motor domain. Analysis of inner ear hair cells by immunohistochemistry, scanning electron microscopy and histology revealed degeneration of hair cells in the inner ear and structural malformation of the stereocilia in the cochlea of Turner homozygous mutant mice. Our data indicate that this novel mouse strain provides a useful model for future studies on the function of myosin VI in mammalian auditory and non-auditory systems and in human syndromes.