OSBPL2-disrupted pigs recapitulate dual features of human hearing loss and hypercholesterolaemia

作     者：Jun Yao Huasha Zeng Min Zhang Qinjun Wei Ying Wang Haiyuan Yang Yajie Lu Rongfeng Li Qiang Xiong Lining Zhang Zhibin Chen Guangqian Xing Xin Cao Yifan Dai Jun Yao;Huasha Zeng;Min Zhang;Qinjun Wei;Ying Wang;Haiyuan Yang;Yajie Lu;Rongfeng Li;Qiang Xiong;Lining Zhang;Zhibin Chen;Guangqian Xing;Xin Cao;Yifan Dai

作者机构：Department of Medical GeneticsSchool of Basic Medical Scienc5Nanjing Medical UniversityNanjing211166China Jiangsu Key Laboratory of XenotransplantationNanjing Medical UniversityNanjing211166China State Key Laboratory of Reproductive Medicin5Department of Prenatal DiagnosisNanjing Maternity and Child Health Care HospitalWomen's Hospital ofNanjing Medical UniversityNanjing210004China The Laboratory Center for Basic Medical SciencesNanjing Medical UniversityNanjing211166China Department of OtolaryngologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2019年第46卷第8期

页      面：379-387页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100213[医学-耳鼻咽喉科学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China (81771000 and 31571302) the Key Research and Development Program of Jiangsu Province (Social Development: BE2016762) the Key Project of Science and Technology Innovation of Nanjing Medical University (2017NJMUCX001) grants from the China Postdoctoral Science Foundation (2016M600431) the Jiangsu Planned Projects for Postdoctoral Research Funds (1601071B) 

主　　题：OSBPL2 Bama miniature pig Hearing loss Hypercholesterolaemia 

摘      要：Oxysterol binding protein like 2(OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotypephenotype associations, the OSBPL2-disrupted Bama miniature(BM) pig model was constructed using CRISPR/Cas9-mediated gene editing, somatic cell nuclear transfer(SCNT) and embryo transplantation approaches, and then subjected to phenotypic characterization of auditory function and serum lipid profiles. The OSBPL2-disrupted pigs displayed progressive hearing loss(HL) with degeneration/apoptosis of cochlea hair cells(HCs) and morphological abnormalities in HC stereocilia, as well as hypercholesterolaemia. High-fat diet(HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia. The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss(NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia.