扬州大学教师个人主页服务平台袁玉国--中文主页-- Hyperhomocysteinemia and dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

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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Hyperhomocysteinemia and dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

点击次数：

影响因子：

3.5

发表刊物：

Lipids Health Dis

摘要：

Background: Congenital hyper-homocysteinemia (HHcy) is caused by a defective cystathionine β-synthase (CBS) gene, and is frequently associated with dyslipdemia. The aim of this study was to further elucidate the effect of mutated CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S point mutation in CBS. Methods: CRISPR/Cas9 system was used to edit the CBS gene in rabbit embryos. The founder rabbits were sequenced, and their plasma homocysteine (Hcy) and lipid profile were analyzed. Results: Six CBS-knockout (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in CBS caused significant growth retardation and high mortality rates within 6 weeks after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) controls. Histological analysis of the mutants showed accumulation of micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric infusion of vitamin B and betaine complex significantly decreased the plasma levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic steatosis compared to the untreated animals. Conclusion: A CBSG307S rabbit model was generated that exhibited severe dyslipidemia when fed on a normal diet, indicating that G307S mutation in the CBS gene is a causative factor for dyslipidemia.

论文类型：

Research Atricle

文献类型：

Research Atricle

是否译文：

否

发表时间：

2020-10-23

收录刊物：

SCI

发布期刊链接：

https://pubmed.ncbi.nlm.nih.gov/33054837/

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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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