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Human apoA‐I/C‐III/A‐IV gene cluster transgenic rabbits: effects of a high‐cholesterol diet
Author(s) -
Recalde Delia,
Baroukh Nadine,
Viglietta Celine,
Prince Sonia,
Verona Julián,
Vergnes Laurent,
Pidoux Josette,
Nazeem Nanjee M,
Brites Fernando,
Ochoa Alberto,
Castro Graciela,
Zakin Mario M,
Miller Norman E,
Marie Houdebine Louis
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.07.041
Subject(s) - medicine , genetically modified mouse , endocrinology , cholesterol , transgene , biology , triglyceride , hypertriglyceridemia , gene , biochemistry
We have generated transgenic rabbits that express the entire human apoA‐I/C‐III/A‐IV gene cluster. As in humans, h‐apoA‐I and h‐apoC‐III were expressed in liver and intestine, whereas h‐apoA‐IV mRNA was detected in intestine only. Transgenic rabbits had significantly higher plasma total cholesterol, HDL‐cholesterol and total phospholipid concentrations than non‐transgenic littermates. In contrast to similar transgenic mice previously generated, which have gross hypertriglyceridemia, triglyceride concentrations were only moderately raised in transgenic rabbits. Plasma and HDL from transgenic rabbits were more effective than those from controls in promoting cholesterol efflux from cultured hepatoma cells. They had lower LCAT, lower CETP and higher PLTP activities than non‐transgenic littermates. Cholesterol‐feeding produced major increases in plasma lipids. The qualitative response to the diet was not modified by cluster expression. Human apoA‐I concentration was halved by cholesterol‐feeding, whereas h‐apoC‐III and h‐apoA‐IV concentrations were not significantly altered. Cholesterol efflux from hepatoma cells to plasma and HDL was not altered by the diet. Since lipoprotein metabolism of rabbits closely resembles that of humans, human apoA‐I/C‐III/A‐IV transgenic rabbits may provide a reliable model for studies of the transcriptional regulation of the cluster, and for evaluating the effects of different agents on the expression of the three genes.