Analysis of deafness using homeobox and molecular motor gene, and knockout mouse

本研究的目的是利用基因敲除小鼠和遗传性耳聋患者分析耳聋的机制。实验动物分别为分子马达和同源异型盒基因突变的小鼠。还研究了具有瘦素基因突变的小鼠。我们发现了Branchio-Oto综合征患者的EYA 1基因突变。已知EYA 1基因与同源框基因如SIX 1基因相关地起作用。本研究表明six 1基因在耳泡的发育和分化过程中起关键作用。Six 1基因敲除小鼠内耳不发育，其表型与SIX 1基因突变的人有很大差异。小鼠和人类之间的这些表型-基因型差异是理解基因功能的先决条件。杰克逊震鼠的sans基因发生了突变，它是一个与分子马达相一致的机械感觉转导通道。瘦素基因敲除小鼠肥胖并患有糖尿病。他们比野生动物还小就聋了。内耳的光镜检查结果显示毛细胞、螺旋神经节细胞和血管纹没有异常，尽管它们的听力水平已经低于正常水平。

The purpose of the present research is to analyze the mechanism of deafness using the knockout mouse and patients with hereditary hearing loss. The experimental animals are mice with mutation of molecular motor and homeobox genes, respectively. The mouse with mutation of the leptin gene was also studied. We identified mutations of EYA1 gene in patients with Branchio-Oto syndrome. EYA1 genes are known to function in association with homeobox genes such as SIX1 gene. The present study demonstrated that six1 gene plays a key role in developing and differentiation of the otic vesicle. Six1 knock out mice showed no development of the inner ear, whose phenotype is quite different from human with mutation of SIX1. These phenotype-genotype difference between mouse and human is prerequisite for understanding the gene function. Jackson shaker mouse is demonstrated to have mutation of the sans, which works as a mechanosensory transduction channel in accordance with molecular motor. Leptin knockout mouse is obese and suffers from diabetes mellitus. They become deaf younger than wild animal. Light microscopic findings of the inner ear showed no abnormality in hair cells, spiral ganglion cells, and stria vascularis, even though their hearing level was already below the normal level.