Transgenic rabbits expressing human lipoprotein lipase

被引：8
作者：
Araki, M
Fan, JL [1 ]
Challah, M
Bensadoun, A
Yamada, N
Honda, K
Watanabe, T
机构：
[1] Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Tsukuba, Ibaraki 3058575, Japan
[2] Cornell Univ, Div Nutr, Ithaca, NY 14853 USA
[3] Univ Tokyo, Dept Internal Med 3, Tokyo 1138655, Japan
[4] Yamanouchi Pharmaceut Co Ltd, Tsukuba Res Ctr, Tsukuba, Ibaraki 3058585, Japan
来源：
CYTOTECHNOLOGY | 2000年 / 33卷 / 1-3期
关键词：
atherosclerosis; lipoprotein; lipoprotein lipase; transgenic rabbit;
D O I：
10.1023/A:1008115429679
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
To study the functions of lipoprotein lipase (LPL) in lipid and lipoprotein metabolism and the relationship between LPL and atherosclerosis, we generated transgenic rabbits expressing the human LPL gene. A total of 4045 Japanese white rabbit embryos were microinjected with a 3.8-kb SalI/HindIII fragment containing the chicken beta-actin promoter, human LPL cDNA and rabbit beta-globin with poly (A) signals, and then transplanted into 116 recipient rabbits. Of the 166 pups born, six pups were transgenic as confirmed by Southern blot analysis. A Northern blot analysis revealed that human LPL was expressed by a number of tissues including the heart, kidney, adrenal gland and intestine. One transgenic rabbit showed up to 3-fold increased LPL activity in post-heparin plasma compared to that in nontransgenic rabbits. Human LPL expression in various tissues of transgenic rabbits was further elucidated by in situ hybridization and immunostaining. Since rabbits are superior to mice as a model of atherosclerosis, this transgenic rabbit model should provide a valuable tool for the study of LPL in lipid metabolism and atherosclerosis.
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页码：93 / 99
页数：7
相关论文
共 29 条
[1]   Immunohistochemical localization of lipoprotein lipase and apolipoprotein E in human atherosclerotic lesions [J].
Araki, M ;
Fan, JL ;
Watanabe, T .
ACTA HISTOCHEMICA ET CYTOCHEMICA, 1998, 31 (06) :485-492
[2]  
BENSADOU.A, 1974, J BIOL CHEM, V249, P2220
[3]   LIPOPROTEIN-LIPASE - CELLULAR-ORIGIN AND FUNCTIONAL DISTRIBUTION [J].
CAMPS, L ;
REINA, M ;
LLOBERA, M ;
VILARO, S ;
OLIVECRONA, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (04) :C673-C681
[4]  
CHALLAH M, 1995, CARDIOVASC RES, V30, P231, DOI 10.1016/0008-6363(96)88516-6
[5]   Transgenic rabbits expressing human apolipoprotein A-I in the liver [J].
Duverger, N ;
Viglietta, C ;
Berthou, L ;
Emmanuel, F ;
Tailleux, A ;
ParmentierNihoul, L ;
Laine, B ;
Fievet, C ;
Castro, G ;
Fruchart, JC ;
Houbebine, LM ;
Denefle, P .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (12) :1424-1429
[6]  
ECKEL RH, 1989, NEW ENGL J MED, V320, P1060
[7]   Increased expression of apolipoprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma [J].
Fan, JL ;
Ji, ZS ;
Huang, YD ;
de Silva, H ;
Sanan, D ;
Mahley, RW ;
Innerarity, TL ;
Taylor, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (10) :2151-2164
[8]   OVEREXPRESSION OF HEPATIC LIPASE IN TRANSGENIC RABBITS LEADS TO A MARKED REDUCTION OF PLASMA HIGH-DENSITY-LIPOPROTEINS AND INTERMEDIATE DENSITY LIPOPROTEINS [J].
FAN, JL ;
WANG, JJ ;
BENSADOUN, A ;
LAUER, SJ ;
DANG, Q ;
MAHLEY, RW ;
TAYLOR, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (18) :8724-8728
[9]   OVEREXPRESSION OF HUMAN APOLIPOPROTEIN B-100 IN TRANSGENIC RABBITS RESULTS IN INCREASED LEVELS OF LDL AND DECREASED LEVELS OF HDL [J].
FAN, JL ;
MCCORMICK, SPA ;
KRAUSS, RM ;
TAYLOR, S ;
QUAN, R ;
TAYLOR, JM ;
YOUNG, SG .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1995, 15 (11) :1889-1899
[10]   PRODUCTION OF TRANSGENIC RABBITS, SHEEP AND PIGS BY MICROINJECTION [J].
HAMMER, RE ;
PURSEL, VG ;
REXROAD, CE ;
WALL, RJ ;
BOLT, DJ ;
EBERT, KM ;
PALMITER, RD ;
BRINSTER, RL .
NATURE, 1985, 315 (6021) :680-683
123