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.

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。