Quantitative trait loci that determine plasma lipids and obesity in C57BL/6J and 129S1/SvlmJ inbred mice

被引:44
作者
Ishimori, N
Li, RH
Kelmenson, PM
Korstanje, R
Walsh, KA
Churchill, GA
Forsman-Semb, K
Paigen, B
机构
[1] Jackson Lab, Bar Harbor, ME 04609 USA
[2] AstraZeneca R&D Molndal, Molndal, Sweden
关键词
body fat mass; body mass index; high-fat diet; non-high density lipoprotein cholesterol; quantitative trait loci; triglyceride;
D O I
10.1194/jlr.M400098-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The plasma lipid concentrations and obesity of C57BL/6J (B6) and 129S1/SvImJ (129) inbred mouse strains fed a high-fat diet containing 15% dairy fat, 1% cholesterol, and 0.5% cholic acid differ markedly. To identify the loci controlling these traits, we conducted a quantitative trait loci (QTL) analysis of 294 (B6 X 129) F-2 females fed a high-fat diet for 14 weeks. Non-HDL cholesterol concentrations were affected by five significant loci: Nhdlq1 [chromosome 8, peak centimorgan (cM) 38, logarithm of odds [LOD] 4.4); Nhdlq4 (chromosome 10, cM 70, LOD 4.0); Nhdlq5 (chromosome 6, cM 0) interacting with Nhdlq4; Nhdlq6 (chromosome 7, cM 10) interacting with Nhdlq1; and Nhdlq7 (chromosome 15, cM 0) interacting with Nhdlq4. Triglyceride (TG) concentrations were affected by three significant loci: Tgq1 (chromosome 18, cM 42, LOD 3.2) and Tgq2 (chromosome 9, cM 66) interacting with Tgq3 (chromosome 4, cM 58). Obesity measured by percentage of body fat mass and body mass index was affected by two significant loci: Obq16 (chromosome 8, cM 48, LOD 10.0) interacting with Obq18 (chromosome 9, cM 65).jlr Knowing the genes for these QTL will enhance our understanding of obesity and lipid metabolism.
引用
收藏
页码:1624 / 1632
页数:9
相关论文
共 36 条
[1]   Using mice to dissect genetic factors in atherosclerosis [J].
Allayee, H ;
Ghazalpour, A ;
Lusis, AJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (09) :1501-1509
[2]  
BIOLA O, 2003, NAT REV GENET, V4, P911
[3]   Cholesterol gallstone formation in overweight mice establishes that obesity per se is not linked directly to cholelithiasis risk [J].
Bouchard, G ;
Johnson, D ;
Carver, T ;
Paigen, B ;
Carey, MC .
JOURNAL OF LIPID RESEARCH, 2002, 43 (07) :1105-1113
[4]   Using mouse models to dissect the genetics of obesity [J].
Brockmann, GA ;
Bevova, MR .
TRENDS IN GENETICS, 2002, 18 (07) :367-376
[5]  
Butler A A, 2001, Trends Genet, V17, pS50, DOI 10.1016/S0168-9525(01)02481-7
[6]  
CHURCHILL GA, 1994, GENETICS, V138, P963
[7]   Genetics and pathophysiology of human obesity [J].
Cummings, DE ;
Schwartz, MW .
ANNUAL REVIEW OF MEDICINE, 2003, 54 :453-471
[8]  
deFaria E, 1996, J LIPID RES, V37, P197
[9]   Quantitative trait loci analysis for plasma HDL-cholesterol concentrations and atherosclerosis susceptibility between inbred mouse strains C57BL/6J and 129S1/SvImJ [J].
Ishimori, N ;
Li, RH ;
Kelmenson, PM ;
Korstanje, R ;
Walsh, KA ;
Churchill, GA ;
Forsman-Semb, K ;
Paigen, B .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (01) :161-166
[10]   Cardiovascular morbidity and mortality associated with the metabolic syndrome [J].
Isomaa, B ;
Almgren, P ;
Tuomi, T ;
Forsén, B ;
Lahti, K ;
Nissén, M ;
Taskinen, MR ;
Groop, L .
DIABETES CARE, 2001, 24 (04) :683-689