Hereditary sensorineural hearing loss in Chinese Rongchang pigs result from promoter mutations in MITF
作者单位：Key Laboratory of Pig Industry Sciences(Ministry of Agriculture)Chongqing Academy of Animal Science Department of OtolaryngologyHead &Neck SurgeryInstitute of OtolaryngologyChinese PLA General Hospital State Key Laboratory for AgrobiotechnologyCollege of Biological SciencesNational Engineering Laboratory for Animal BreedingChina Agricultural University
会议名称：《第七届中国畜牧科技论坛》
会议日期：2016年
关 键 词：de novo silencer MITF-M hearing loss Waardenburg syndrome cisregulatory element pig
摘 要：(Background) Genesis of novel gene regulatorymodules is largely responsible formorphological and functional *** active cisz-regulatory elements(CREs) can arise from transposition,promoter switching,co-option or de novo ***,the last model,de novo genesis of CREs could be a rare event in genome evolution,due to the odds of creating totally novel CREs aremuch lower than that of altering existing *** is only reported by a sole case in ***,genetic variation drives either new genesis of CREs or phenotypic alteration has not been ***:Here,we took advantage of a spontaneous hearing loss model found in pigs,and studied the mutation in a non-regulatory region of the melanocyte-specific promoter of microphthalmia-associated transcription factor(MITF) *** mutation generated a novel silencer and eliminated expression of *** consequently caused the early degeneration of intermediate cells of the cochlear stria vascularis and profound hearing loss,similar to the typical phenotype of Waardenburgsyndrome in *** found that the mutation exclusively affected MITF-M,not other *** essential function of Mitf-m in hearing development was further validated using a knock-out mouse ***:These results demonstrated that dysfunction in the MITF-M isoform alone was sufficient to cause deafness and *** our knowledge,this study provides the first evidence of a systemic functional de novo CRE in mammals.