Advertisement
Research Article Free access | 10.1172/JCI116728
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100.
Find articles by Fazio, S. in: JCI | PubMed | Google Scholar
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100.
Find articles by Lee, Y. in: JCI | PubMed | Google Scholar
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100.
Find articles by Ji, Z. in: JCI | PubMed | Google Scholar
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100.
Find articles by Rall, S. in: JCI | PubMed | Google Scholar
Published September 1, 1993 - More info
Transgenic mice were prepared that expressed a dysfunctional apo E variant, apo E (Arg-112, Cys-142), which is associated with dominant inheritance of type III hyperlipoproteinemia (type III HLP) in humans. Among eight founder mice, plasma apo E (Arg-112, Cys-142) levels varied 100-fold and directly correlated with plasma cholesterol and triglyceride levels. On a normal chow diet, mice expressing high levels (> 70 mg/dl) of the dysfunctional apo E had grossly elevated plasma lipids, with cholesterol levels of up to 410 mg/dl and triglyceride levels of up to 1,210 mg/dl. Upon agarose electrophoresis, plasma from these mice demonstrated beta-very low density lipoproteins (beta-VLDL). Mice expressing low (< 2.5 mg/dl) or intermediate (21 mg/dl) levels of the apo E variant had much less severe hyperlipidemia and did not have beta-VLDL. Although the transgenic mouse beta-VLDL were enriched in cholesteryl esters compared with normal mouse VLDL, they were not as cholesterol enriched as human beta-VLDL from type III HLP subjects. Transgenic mouse beta-VLDL injected into normal mice were cleared from plasma at a significantly slower rate than normal mouse VLDL, demonstrating the impaired catabolism of beta-VLDL. Thus, transgenic mice expressing high levels of the dysfunctional apo E (Arg-112, Cys-142) variant have many characteristics of the human type III HLP phenotype and appear to be a suitable animal model for this disorder.
Images.