Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoprotein CIII

Authors

  • Jingyuan Wei,

    1.  Laboratory Animal Center, Jilin University, Changchun, China
    2.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    3.  Liaoning Province Academy of Analytic Science, Shenyang, China
    4.  Center for Animal Embryo Engineering of Jilin Province, Changchun, China
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    • These authors contributed equally to this work

  • Hongsheng Ouyang,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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    • These authors contributed equally to this work

  • Yuhui Wang,

    1.  Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China
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    • These authors contributed equally to this work

  • Daxin Pang,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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    • These authors contributed equally to this work

  • Nathan X. Cong,

    1.  Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China
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  • Tiedong Wang,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Bingfeng Leng,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Dong Li,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Xiaoping Li,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Rong Wu,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Yu Ding,

    1.  Laboratory Animal Center, Jilin University, Changchun, China
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  • Fei Gao,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Yanhong Deng,

    1.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Bo Liu,

    1.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Ziyi Li,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Liangxue Lai,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
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  • Haihua Feng,

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
    3.  Institute of Zoonesis, Jilin University, Changchun, China
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  • George Liu,

    1.  Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, China
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  • Xuming Deng

    1.  Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, China
    2.  College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China
    3.  Institute of Zoonesis, Jilin University, Changchun, China
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G. Liu, Institute of Cardiovascular Science, Peking University Health Science Center, Xueyuan Road 38, Haidian District, Beijing 100191, China
Fax: +86 10 82802769
Tel: +86 10 82802769
E-mail: vangeorgeliu@gmail.com; georgeliu@bjmu.edu.cn
X. Deng, College of Animal Science and Veterinary Medicine, Jilin University, Xi’an Road 5333, Changchun 130062, China
Fax: +86 431 87836160
Tel: +86 431 87836161
E-mail: xumingdeng@yahoo.com.cn; dengxm@jlu.edu.cn

Abstract

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.

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