自发色素异常综合征型耳聋突变豪猪新模型的建立及其特性研究

Deafness is the second disabling disease in China, over 50% caused by genetic factors. Hereditary hearing loss has a high degree of genetic heterogeneity, but mostly belongs to sensorineural hearing loss. At present, it lacks effective treatments and lacks large animal models which are more similar in genetic and disease characteristics, and more suitable for surgical operation and clinical and translational research in the study. In the pre-study, a spontaneous mutant porcupine of syndromic heredity hearing loss associated with pigmentary abnormalities was obtained. In this project, we are planning to establish a genetic stable and individual uniform porcupine family with hearing loss through the mutation individual breeding, then test the individual in pigment pathological examination, otology clinical detection and inner ear morphology analysis and other systematic clinical characteristics identification and systematic identification of the phenotype features; use the homologous cloning and RACE technology to amplify and clone porcupine pathogenic candidate gene full-length sequence cDNA, and further through sequencing to make sure the mutant gene and its mutations, and to identify the genetic characteristics of the mutation. Accordingly, a new large animal model with genetic stability and definit biological characteristic for human hereditary hearing loss will be created as important research tools in pathogenesis, clinical treatment and evaluation of drug and medical devices of human genetic hearing loss.

耳聋是我国第二大致残疾病，50%以上由遗传因素引起。遗传性耳聋具有高度遗传异质性，但多属感音神经性耳聋，目前缺乏有效的治疗方法且在其研究上缺乏与人在遗传及疾病特性上更相似的、适于外科操作和临床转化研究的大动物模型。本课题拟在前期获得自发色素异常综合征型遗传性耳聋突变豪猪的基础上，将突变个体扩群繁育建立大家系，对家系内个体进行色素病理学检测、耳科临床检测、内耳形态学分析等系统临床特性鉴定，系统鉴定其表型特征；利用同源克隆和RACE技术扩增和克隆豪猪致病候选基因全长cDNA序列，进一步通过测序确定突变基因及其突变位点，鉴定该突变的遗传特性。本研究将创建新的遗传稳定、生物学特性明确的人类遗传性耳聋大动物模型，为人类遗传性耳聋致病机理研究、临床干预治疗及医疗器械评价等提供重要工具和材料。