Premium
Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoprotein CIII
Author(s) -
Wei Jingyuan,
Ouyang Hongsheng,
Wang Yuhui,
Pang Daxin,
Cong Nathan X.,
Wang Tiedong,
Leng Bingfeng,
Li Dong,
Li Xiaoping,
Wu Rong,
Ding Yu,
Gao Fei,
Deng Yanhong,
Liu Bo,
Li Ziyi,
Lai Liangxue,
Feng Haihua,
Liu George,
Deng Xuming
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08401.x
Subject(s) - hypertriglyceridemia , medicine , endocrinology , triglyceride , chylomicron , apolipoprotein b , transgene , lipoprotein , genetically modified mouse , lipoprotein lipase , biology , cholesterol , high density lipoprotein , very low density lipoprotein , biochemistry , gene , adipose tissue
Hypertriglyceridemia has recently been considered to be an independent risk factor for coronary heart disease, in which apolipoprotein (Apo)CIII is one of the major contributory factors, as it is strongly correlated with plasma triglyceride levels. Although ApoCIII transgenic mice have been generated as an animal model for the study of hypertriglyceridemia, the features of lipoprotein metabolism in mice differ greatly from those in humans. Because of the great similarity between pigs and humans with respect to lipid metabolism and cardiovascular physiology, we generated transgenic miniature pigs expressing human ApoCIII by the transfection of somatic cells combined with nuclear transfer. The expression of human ApoCIII was detected in the liver and intestine of the transgenic pigs. As compared with nontransgenic controls, transgenic pigs showed significantly increased plasma triglyceride levels (83 ± 36 versus 38 ± 4 mg·dL −1 , P < 0.01) when fed a chow diet. Plasma lipoprotein profiling by FPLC in transgenic animals showed a higher peak in large‐particle fractions corresponding to very low‐density lipoprotein/chylomicrons when triglyceride content in the fractions was assayed. There was not much difference in cholesterol content in FPLC fractions, although a large low‐density lipoprotein peak was identified in both nontransgenic and transgenic animals, resembling that found in humans. Further analysis revealed markedly delayed clearance of plasma triglyceride, accompanied by significantly reduced lipoprotein lipase activity in post‐heparin plasma, in transgenic pigs as compared with nontransgenic controls. In summary, we have successfully generated a novel hypertriglyceridemic ApoCIII transgenic miniature pig model that could be of great value for studies on hyperlipidemia in relation to atherosclerotic disorders.