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来分析耳聋的机制。实验动物分别是分子马达和同源盒基因突变的小鼠。瘦素基因突变的小鼠也被研究了。我们在Branchio-Oto综合征患者中发现了EYA1基因突变。已知EYA1基因的功能与SIX1基因等同源框基因相关。本研究表明SIX1基因在耳囊的发育和分化中起关键作用。SIX1基因敲除小鼠的内耳没有发育，其表型与人类SIX1基因突变有很大不同。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前提。Jackson Shaker小鼠被证实存在SANS突变，SANS是根据分子马达作为机械感觉转导通道发挥作用的。瘦素基因敲除小鼠肥胖，并患有糖尿病。他们比野生动物还年轻就变聋了。内耳光镜检查发现，毛细胞、螺旋神经节细胞和血管纹未见异常，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.