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OSBPL2-disrupted pigs recapitulate dual features of human hearing loss and hypercholesterolaemia.
Journal of Genetics and Genomics ( IF 6.6 ) Pub Date : 2019-08-13 , DOI: 10.1016/j.jgg.2019.06.006
Jun Yao 1 , Huasha Zeng 2 , Min Zhang 3 , Qinjun Wei 4 , Ying Wang 1 , Haiyuan Yang 1 , Yajie Lu 1 , Rongfeng Li 1 , Qiang Xiong 5 , Lining Zhang 5 , Zhibin Chen 6 , Guangqian Xing 6 , Xin Cao 4 , Yifan Dai 1
Affiliation  

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.



中文翻译:

OSBPL2破坏的猪概括了人类听力损失和高胆固醇血症的双重特征。

氧固醇结合蛋白2(OSBPL2)是细胞脂质代谢和运输中的重要调节剂,在我们以前的研究中被确定为一种新型的耳聋致病基因。为类似的表型特征OSBPL2突变的动物模型和阐明潜在的基因型-表型协会,OSBPL2 -disrupted巴马(BM)猪模型是使用CRISPR / Cas9介导的基因编辑,体细胞核转移(SCNT)构建和胚胎移植方法,然后进行听觉功能和血脂水平的表型表征。该OSBPL2受损的猪表现出进行性听力丧失(HL),并伴有耳蜗毛细胞(HCs)的变性/凋亡,HC立体纤毛的形态异常以及高胆固醇血症。高脂饮食(HFD)会加剧HL的发展,并导致更严重的高胆固醇血症。在OSBPL2中断的猪中类似的进行性HL和高胆固醇血症的双重表型证实了OSBPL2突变与非症状性听力损失(NSHL)有关,并且有助于听觉功能障碍和血脂异常/高胆固醇血症之间的潜在联系。

更新日期:2019-08-13
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