扬州大学教师个人主页服务平台袁玉国--中文主页-- Spontaneous severe hypercholesterolemia and atherosclerosis lesions in rabbits with deficiency of low-density lipoprotein receptor (LDLR) on exon 7

袁玉国

学位：博士
职称：副高级
所在单位：兽医学院

博士生导师

硕士生导师

教师英文名称：Yuguo Yuan
教师拼音名称：Yuan Yuguo
电子邮箱：
入职时间：2010-06-01
学历：博士研究生毕业
办公地点：扬州大学文汇路校区45楼102室
性别：男
联系方式：0514-87979228
在职信息：在岗
毕业院校：扬州大学

学科：临床兽医学

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Spontaneous severe hypercholesterolemia and atherosclerosis lesions in rabbits with deficiency of low-density lipoprotein receptor (LDLR) on exon 7

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影响因子：

8.3

发表刊物：

EBioMedicine

摘要：

Rabbits (Oryctolagus cuniculus) have been the very frequently used as animal models in the study of human lipid metabolism and atherosclerosis, because they have similar lipoprotein metabolism to humans. Most of hyperlipidemia and atherosclerosis rabbit models are produced by feeding rabbits a high-cholesterol diet. Gene editing or knockout (KO) offered another means of producing rabbit models for study of the metabolism of lipids and lipoproteins. Even so, apolipoprotein (Apo)E KO rabbits must be fed a high-cholesterol diet to induce hyperlipidemia. In this study, we used the CRISPR/Cas9 system anchored exon 7 of low-density lipoprotein receptor (LDLR) in an attempt to generate KO rabbits. We designed two sgRNA sequences located in E7:g.7055-7074 and E7:g.7102-7124 of rabbit LDLR gene, respectively. Seven LDLR-KO founder rabbits were generated, and all of them contained biallelic modifications. Various mutational LDLR amino acid sequences of the 7 founder rabbits were subjected to tertiary structure modeling with SWISS-MODEL, and results showed that the structure of EGF-A domain of each protein differs from the wild-type. All the founder rabbits spontaneously developed hypercholesterolemia and atherosclerosis on a normal chow (NC) diet. Analysis of their plasma lipids and lipoproteins at the age of 12 weeks revealed that all these KO rabbits exhibited markedly increased levels of plasma TC (the highest of which was 1013.15 mg/dl, 20-fold higher than wild-type rabbits), LDL-C (the highest of which was 730.00 mg/dl, 35-fold higher than wild-type rabbits) and TG accompanied by reduced HDL-C levels. Pathological examinations of a founder rabbit showed prominent aortic atherosclerosis lesions and coronary artery atherosclerosis.In conclusion, we have reported the generation LDLR-KO rabbit model for the study of spontaneous hypercholesterolemia and atherosclerosis on a NC diet. The LDLR-KO rabbits should be a useful rabbit model of human familial hypercholesterolemia (FH) for the simulations of human primary hypercholesterolemia and such models would allow more exact research into cardio-cerebrovascular disease.

是否译文：

否

发表时间：

2018-12-23

收录刊物：

SCI

发布期刊链接：

https://pubmed.ncbi.nlm.nih.gov/30243490/

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下一条： Efficient increase of the novel recombinant human plasminogen activator expression level and stability through the use of homozygote transgenic rabbits

个人简介

袁玉国，博士，副教授，硕士、博士生导师。2010年毕业于扬州大学兽医学院，获临床兽医学博士学位，并留校任教。2015.10—2017.7韩国Konkuk University博士后，2017.9—2018.9韩国Gyeongsang National University访问学者。

长期从事动物体细胞克隆和转基因克隆的研究工作，2007年在国内外首次报道利用成年乳腺上皮细胞获得克隆山羊，先后获得转人乳铁蛋白，白蛋白等转基因克隆羊。利用TALEN，Cas9技术获得Fel d1基因敲除猫、MSTN基因敲除山羊，人高血脂兔动物模型（兔）等。同时开展了功能纳米材料的制备及其在抗菌、抗肿瘤和化妆品上的应用。先后主持了国家自然科学基金、国家转基因重大专项子课题、江苏省种业“揭榜挂帅”等15余项课题的研究工作，在 EBioMedicine，Int J Nanomedicine，Cells，Oxid Med Cell Longev, Int J Mol Sci，Mol Reprod Dev，Theriogenology等杂志发表SCI论文30余篇，获得省部级等科技奖励2项、发明专利1项。

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