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Titolo:
Genetic control of HDL levels and composition in an interspecific mouse cross (CAST/Ei x C57BL/6J)
Autore:
Mehrabian, M; Castellani, LW; Wen, PZ; Wong, J; Rithaporn, T; Hama, SY; Hough, GP; Johnson, D; Albers, JJ; Mottino, GA; Frank, JS; Navab, M; Fogelman, AM; Lusis, AJ;
Indirizzi:
Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA Univ Calif LosAngeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Washington, NW Lipid Labs, Seattle, WA 98115 USA Univ Washington Seattle WA USA 98115 NW Lipid Labs, Seattle, WA 98115 USA Univ Washington, Dept Med, Seattle, WA 98115 USA Univ Washington Seattle WA USA 98115 ton, Dept Med, Seattle, WA 98115 USA
Titolo Testata:
JOURNAL OF LIPID RESEARCH
fascicolo: 12, volume: 41, anno: 2000,
pagine: 1936 - 1946
SICI:
0022-2275(200012)41:12<1936:GCOHLA>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH-DENSITY-LIPOPROTEINS; CHOLESTEROL ACYLTRANSFERASE GENE; BINDING CASSETTE TRANSPORTER-1; APOLIPOPROTEIN-A-II; TANGIER-DISEASE; TRANSGENIC MICE; COMPLEX TRAITS; BODY-FAT; METABOLISM; MODEL;
Keywords:
quantitative trait locus mapping lecithin : cholesterol acyltransferase adrenal lipid depletion; scavenger receptor BI; phospholipid transfer protein; apolipoprotein A-I; cholesterol-7 alpha-hydroxylase; high fat diet;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Lusis, AJ Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA UnivCalif Los Angeles Los Angeles CA USA 90095 s, CA 90095 USA
Citazione:
M. Mehrabian et al., "Genetic control of HDL levels and composition in an interspecific mouse cross (CAST/Ei x C57BL/6J)", J LIPID RES, 41(12), 2000, pp. 1936-1946

Abstract

Strain CAST/Ei (CAST) mice exhibit unusually low levels of high density lipoproteins (HDL) as compared with most other strains of mice, including C57BL/6J (B6). This appears to be due in part to a functional deficiency of lecithin:cholesterol acyltransferase (LCAT). LCAT mRNA expression in CAST mice is normal, but the mice exhibit several characteristics consistent with functional deficiency. First, the activity and mass of LCAT in plasma and inHDL of CAST mice were reduced significantly. Second, the HDL of CAST mice were relatively poor in phospholipids and cholesteryl esters, but rich in free cholesterol and apolipoprotein A-I (apoA-I). Third, the adrenals of CAST mice were depleted of cholesteryl esters, a phenotype similar to that observed in LCAT- and acyl-CoA:cholesterol acyltransferase-deficient mice. Fourth, in common with LCAT-deficient mice, CAST mice contained triglyceride-rich lipoproteins with "panhandle"-like protrusions. To examine the genetic bases of these differences, we studied HDL lipid levels in an intercross between strain CAST and the common laboratory strain B6 on a low fat, chow diet as well as a high fat, atherogenic diet. HDL levels exhibited complex inheritance, as 12 quantitative trait loci with significant or suggestive likelihood of observed data scores were identified. Several of the loci occurred over plausible candidate genes and these were investigated. The results indicate that the functional LCAT deficiency is unlikely to be due to variations of the LCAT gene. Our results suggest that novel genes are Likely to be important in the control of HDL metabolism, and they provide evidence ofgenetic factors influencing the interaction of LCAT with HDL.

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Documento generato il 30/03/20 alle ore 12:14:02