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

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

doi:10.1016/j.jgg.2019.06.006

Volume 46 Issue 8

Aug. 2019

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Article Navigation > Journal of Genetics and Genomics > 2019 > 46(8): 379-387

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

doi: 10.1016/j.jgg.2019.06.006

Jun Yao^{a, b, #},
Huasha Zeng^{a, c, #},
Min Zhang^a,
Qinjun Wei^{a, b, d},
Ying Wang^{a, b},
Haiyuan Yang^{a, b},
Yajie Lu^{a, b},
Rongfeng Li^{a, b},
Qiang Xiong^b,
Lining Zhang^b,
Zhibin Chen^e,
Guangqian Xing^e,
Xin Cao^{a, b, d},
Yifan Dai^{a, b}

a
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, 211166, China
b
Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China
c
State 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
d
The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China
e
Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

More Information

Corresponding 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.
- Bama miniature pig,
- Hearing loss,
- Hypercholesterolaemia

These authors contributed equally to this work.

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References(42)

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