Targeted deletion of Math6 results in severe hearing loss in mice
Targeted deletion of Math6 results in severe hearing loss in mice
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Math6 的定向删除导致小鼠严重听力损失
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通讯作者：
Lin Gan
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作者：
Qi Tang 唐琦;Yong-li Zhang 张永丽;Hua Yang 杨华;Xiao-hui Zhu 朱晓晖;Juan-juan Gao 高娟娟;Zhi-qiang Gao 高志强;Xiao-xia Zhu;Robert D. Frisina;Lin Gan
Math6，也被称为Atoh8，是一种bHLH基因，据报道在发育中的神经系统、胰腺和肾脏中具有重要功能。然而，其在内耳中的表达模式和功能尚不清楚。为了研究Math6在发育中的小鼠内耳中的功能，我们产生了杂合的Math6lacZ/+小鼠系，并通过杂交Math6lacZ/+小鼠获得了Math6的靶向缺失。我们研究了Math6在内耳中的表达模式，发现了一个有趣的结果：Math6-null （Math6lacZ/lacZ）小鼠存活，但比其窝友小，并且听力测试（ABR， DOPAE）证实严重耳聋。我们通过杂交Math6lacZ/+小鼠从18窝中采集了129只存活的新生儿，经χ2检验发现Math6lacZ/+、Math6lacZ/lacZ和wide型的分布与预期的中位数比非常接近。然而，在塑料切片和电子显微镜下，突变小鼠耳蜗未见明显的形态学变化。Myosin6、Prestin、TrkC、GAD65、Tuj1和Calretinin的表达在突变小鼠与对照组之间无显著差异。这表明Math6在正常听力发育中起着重要作用，但其在听力中的确切功能还有待进一步研究。
Math6, also named as Atoh8, is a bHLH gene reported to have important functions in the developing nervous system, pancreas and kidney. However, its expression pattern and function in the inner ear are still unclear. To study the function of Math6 in the developing mouse inner ear, we generated heterozygous Math6lacZ/+ mice line and obtained targeted deletion of Math6 by intercrossing Math6lacZ/+ mice. We studied the expression pattern of Math6 in inner ear and found the interesting result that Math6-null (Math6lacZ/lacZ) mice are viable but smaller than their littermates and are severely deafened with confirmation by hearing test (ABR, DOPAE). We collected 129 viable newborns from 18 litters by crossing Math6lacZ/+ mice and found that the distribution of Math6lacZ/+, Math6lacZ/lacZ and wide type are very close to the expected Medelian ratio by χ2 testing. However, no remarkable morphological changes of cochleae in mutant mice were detected under plastic section and electron microscopy. And no remarkable difference of expressions of Myosin6, Prestin, TrkC, GAD65, Tuj1 and Calretinin were detected between the mutant mice and the control mice. It indicates that Math6 plays important role in development of normal hearing while further studies are required to elucidate its exact function on hearing.