Tags

Type your tag names separated by a space and hit enter

Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia.
J Biol Chem. 1993 May 15; 268(14):10540-5.JB

Abstract

Apolipoprotein (apo) E3-Leiden, described in a large Dutch family, is associated with a dominantly inherited form of familial dysbetalipoproteinemia. To study the effect of the APOE*3-Leiden mutation in vivo, transgenic mice were generated using a genomic 27-kilobase DNA construct isolated from the APOE*3-Leiden proband. This construct carried the APOE gene, the APOC1 gene, and all known regulatory elements including an element that mediates liver expression. Three strains were generated that showed human APOE and APOC1 expression. All strains had significantly elevated levels of total plasma cholesterol and triglycerides on a regular diet. When mice of one strain were fed a semisynthetic cholesterol-rich diet, total plasma cholesterol and triglyceride levels increased dramatically. This increase was observed mainly in the very low density lipoprotein (VLDL)- and low density lipoprotein (LDL)-sized fractions. In cholesterol-fed mice, the apoE3-Leiden protein became equally distributed between the VLDL/LDL and HDL-sized fractions, while in mice kept on a regular diet, apoE3-Leiden protein was mainly associated with HDL-sized fractions. The presence of hyperlipoproteinemia in the APOE*3-Leiden-expressing transgenic mice supports our finding that the apoE3-Leiden variant behaves like a dominant trait in the expression of familial dysbetalipoproteinemia. ApoE3-Leiden transgenic mice may serve as a model to elucidate additional factors involved in the metabolism of apoE containing remnant lipoproteins in general and the etiology of familial dysbetalipoproteinemia in particular.

Authors+Show Affiliations

MGC-Department of Human Genetics, Leiden University, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7683682

Citation

van den Maagdenberg, A M., et al. "Transgenic Mice Carrying the Apolipoprotein E3-Leiden Gene Exhibit Hyperlipoproteinemia." The Journal of Biological Chemistry, vol. 268, no. 14, 1993, pp. 10540-5.
van den Maagdenberg AM, Hofker MH, Krimpenfort PJ, et al. Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. J Biol Chem. 1993;268(14):10540-5.
van den Maagdenberg, A. M., Hofker, M. H., Krimpenfort, P. J., de Bruijn, I., van Vlijmen, B., van der Boom, H., Havekes, L. M., & Frants, R. R. (1993). Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. The Journal of Biological Chemistry, 268(14), 10540-5.
van den Maagdenberg AM, et al. Transgenic Mice Carrying the Apolipoprotein E3-Leiden Gene Exhibit Hyperlipoproteinemia. J Biol Chem. 1993 May 15;268(14):10540-5. PubMed PMID: 7683682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. AU - van den Maagdenberg,A M, AU - Hofker,M H, AU - Krimpenfort,P J, AU - de Bruijn,I, AU - van Vlijmen,B, AU - van der Boom,H, AU - Havekes,L M, AU - Frants,R R, PY - 1993/5/15/pubmed PY - 1993/5/15/medline PY - 1993/5/15/entrez SP - 10540 EP - 5 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 268 IS - 14 N2 - Apolipoprotein (apo) E3-Leiden, described in a large Dutch family, is associated with a dominantly inherited form of familial dysbetalipoproteinemia. To study the effect of the APOE*3-Leiden mutation in vivo, transgenic mice were generated using a genomic 27-kilobase DNA construct isolated from the APOE*3-Leiden proband. This construct carried the APOE gene, the APOC1 gene, and all known regulatory elements including an element that mediates liver expression. Three strains were generated that showed human APOE and APOC1 expression. All strains had significantly elevated levels of total plasma cholesterol and triglycerides on a regular diet. When mice of one strain were fed a semisynthetic cholesterol-rich diet, total plasma cholesterol and triglyceride levels increased dramatically. This increase was observed mainly in the very low density lipoprotein (VLDL)- and low density lipoprotein (LDL)-sized fractions. In cholesterol-fed mice, the apoE3-Leiden protein became equally distributed between the VLDL/LDL and HDL-sized fractions, while in mice kept on a regular diet, apoE3-Leiden protein was mainly associated with HDL-sized fractions. The presence of hyperlipoproteinemia in the APOE*3-Leiden-expressing transgenic mice supports our finding that the apoE3-Leiden variant behaves like a dominant trait in the expression of familial dysbetalipoproteinemia. ApoE3-Leiden transgenic mice may serve as a model to elucidate additional factors involved in the metabolism of apoE containing remnant lipoproteins in general and the etiology of familial dysbetalipoproteinemia in particular. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/7683682/Transgenic_mice_carrying_the_apolipoprotein_E3_Leiden_gene_exhibit_hyperlipoproteinemia_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=7683682 DB - PRIME DP - Unbound Medicine ER -