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Titolo:
Two novel quantitative trait loci on mouse chromosomes 6 and 4 independently and synergistically regulate plasma apoB levels
Autore:
Ko, C; Lee, TL; Lau, PW; Li, J; Davis, BT; Voyiaziakis, E; Allison, DB; Chua, SC; Huang, LS;
Indirizzi:
Columbia Univ, Coll Phys & Surg, Inst Human Nutr, New York, NY 10032 USA Columbia Univ New York NY USA 10032 st Human Nutr, New York, NY 10032 USA Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA ColumbiaUniv New York NY USA 10032 urg, Dept Med, New York, NY 10032 USA Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA Columbia Univ New York NY USA 10032 , Dept Pediat, New York, NY 10032 USA Columbia Univ, Coll Phys & Surg, Obes Res Ctr, St Lukes Roosevelt Hosp, New York, NY 10025 USA Columbia Univ New York NY USA 10025 oosevelt Hosp, New York, NY 10025 USA
Titolo Testata:
JOURNAL OF LIPID RESEARCH
fascicolo: 5, volume: 42, anno: 2001,
pagine: 844 - 855
SICI:
0022-2275(200105)42:5<844:TNQTLO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY-LIPOPROTEIN; FAMILIAL COMBINED HYPERLIPIDEMIA; ACTIVATED RECEPTOR-GAMMA; B-CONTAINING LIPOPROTEINS; HUMAN APOLIPOPROTEIN-B; MESSENGER-RNA; CHOLESTEROL LEVELS; TRANSGENIC MICE; MAJOR LOCUS; GENE;
Keywords:
genetics; mapping; apoB secretion; hypobetalipoproteinemia; familial combined hyperlipidemia; inbred mouse strains;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Huang, LS Columbia Univ, Coll Phys & Surg, Inst Human Nutr, 630 W 168th St,PH 10-305, New York, NY 10032 USA Columbia Univ 630 W 168th St,PH 10-305 New York NY USA 10032 USA
Citazione:
C. Ko et al., "Two novel quantitative trait loci on mouse chromosomes 6 and 4 independently and synergistically regulate plasma apoB levels", J LIPID RES, 42(5), 2001, pp. 844-855

Abstract

An elevated plasma apolipoprotein B (apoB) level is a strong predictor of atherosclerosis and coronary heart disease. Epidemiologic and family linkage studies have suggested a genetic basis for the wide variations of plasma apoB levels In the general population, Using a human apoB transgenic (HuBTg) mouse model, we have previously shown that hepatic apoB-100 secretion is a major determinant of the high and low plasma human apoB levels in HuBTg mice of the C57BL/6 (B6) and 129/Sv (129) strains, respectively, In the present article, we present the identification of two novel quantitative trait loci (QTL) as major regulators of plasma human apoB levels in the Fz and Ng(backcrossed) offspring (n = 572) derived from crosses between the B6 and 129 mouse strains. These loci were designated ApoB regulator genes (Abrg), because the gene products are Likely to be involved in the regulation of plasma apoB levels either directly or indirectly, The first locus, designatedAbrg1, was mapped to chromosome 6 in 8-week-old male and female mice with a combined logarithm of odds ratio (LOD) score of 14 at the D6Mit55 marker (similar to 45.9 cM). Abrg1 contributed approximately 35% of the genetic variance. The second locus, designated Abrg2, was mapped to chromosome 4 withan LOD score of 8.6 in 8-week-old male mice but an LOD score of only 2.0 in 8-week-old female mice at the D4Mit27 marker (similar to 35 cM), Abrg2 contributed approximately 26% of the genetic variance. Epistasis between Abrg1 and Abrg2 was defected and accounted for approximately 12% of the geneticvariance. The combination of these two QTL has major effects (> 70%) on the regulation of plasma human apoB levels in the tested population. In summary, we have identified two novel loci that have a major role in the regulation of plasma apoB levels and are likely to regulate tire secretory pathwayof apoB, The human orthologs for the Abrg loci are strong candidates for human disorders characterized by altered plasma apoB levels, such as FCHL and familial hypobetalipoproteinemia. - Ko, C., T-L. Lee, P. W. Lau, J. Li, B. T. Davis, E. Voyaziakis, D. B. Allison, S. C. Chua,Jr:, and L-S. Huang. Two novel quantitative trait loci on mouse chromosomes 6 and 4 independentlyand synergistically regulate plasma apoB levels.

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Documento generato il 29/03/20 alle ore 09:24:45