Expression of human apoAII in transgenic rabbits leads to dyslipidemia: a new model for combined hyperlipidemia.
OBJECTIVE
Apolipoprotein AII (apoAII) is the second major apolipoprotein in high-density lipoprotein (HDL). However, the physiological functions of apoAII in lipoprotein metabolism have not been fully elucidated.


RESULTS
We generated human apoAII transgenic (Tg) rabbits, a species that normally does not have an endogenous apoAII gene. Plasma levels of human apoAII in Tg rabbits were approximately 30 mg/dL, similar to the plasma levels in healthy humans. The expression of human apoAII in Tg rabbits resulted in increased levels of plasma triglycerides, total cholesterol, and phospholipids accompanied by a marked reduction in HDL-cholesterol levels compared with non-Tg littermates. Analysis of lipoprotein fractions showed that hyperlipidemia exhibited by Tg rabbits was caused by elevated levels of very-low-density lipoproteins (VLDL) and intermediate-density lipoproteins. Furthermore, postheparin lipoprotein lipase activity significantly decreased in Tg rabbits compared with non-Tg rabbits.


CONCLUSIONS
These results indicate that apoAII plays an important role in both VLDL and HDL metabolism, possibly through the inhibition of lipoprotein lipase activity. ApoAII Tg rabbits may become a new model for the study of human familial combined hyperlipidemia.
Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan.
Tomonari
T
Koike
Shuji
S
Kitajima
Ying
Y
Yu
Ying
Y
Li
Kazutoshi
K
Nishijima
Enqi
E
Liu
Huijun
H
Sun
Ahmed Bilal
AB
Waqar
Nobumitsu
N
Shibata
Tomoriho
T
Inoue
Yao
Y
Wang
Bo
B
Zhang
Junji
J
Kobayashi
Masatoshi
M
Morimoto
Keijiro
K
Saku
Teruo
T
Watanabe
Jianglin
J
Fan
D000818:Animals; D030801:Animals, Genetically Modified; D016633:Apolipoprotein A-II / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000209:etiology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000097:blood; D053419:Lipoproteins, IDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D011994:Recombinant Proteins; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase