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
aDepartment of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China
bJiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China
cState Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, 210004, China
dThe Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China
eDepartment of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
More InformationCorresponding author: E-mail address: caoxin@njmu.edu.cn (Xin Cao);E-mail address: daiyifan@njmu.edu.cn (Yifan Dai)
Received Date: 2019-03-12
Accepted Date:2019-06-04
Rev Recd Date:2019-06-03
Available Online: 2019-08-13 Publish Date:2019-08-20
Abstract
Abstract
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 genotype-phenotype 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.Keywords: Bama miniature pig,
Hearing loss,
Hypercholesterolaemia
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