Publication Details

Two novel quantitative trait loci on mouse chromosomes 6 and 4 independently and synergistically regulate plasma apoB levels.

Authors:Ko C, Lee TL, Lau PW, Li J, Davis BT, Voyiaziakis E, Allison DB, Chua SC Jr, Huang LS
Title:Two novel quantitative trait loci on mouse chromosomes 6 and 4 independently and synergistically regulate plasma apoB levels.
Journal:Journal of lipid research May 2001 , Vol 42 , pp. 844-55
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 F(2) and N(2) (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, designated Abrg1, 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 ( approximately 45.9 cM). Abrg1 contributed approximately 35% of the genetic variance. The second locus, designated Abrg2, was mapped to chromosome 4 with an 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 ( approximately 35 cM). Abrg2 contributed approximately 26% of the genetic variance. Epistasis between Abrg1 and Abrg2 was detected and accounted for approximately 12% of the genetic variance. 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 the secretory pathway of 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.   PUBMED: 11352992
Ontological Annotations:
  • MP:0005338: atherosclerotic lesions (Publication, NCBO Annotator)
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator)
  • D006801: Humans (Publication, NCBO Annotator)
  • D002875: Chromosomes (Publication, NCBO Annotator)
  • D007062: Identification (Psychology) (Publication, NCBO Annotator)
  • D005809: Genes, Regulator (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • D055571: Secretory Pathway (Publication, NCBO Annotator)
  • D012634: Bodily Secretions (Publication, NCBO Annotator)
  • D008126: Lod Score (Publication, NCBO Annotator)
  • D050197: Atherosclerosis (Publication, NCBO Annotator)
  • GO:0005694: chromosome (Publication, NCBO Annotator)
  • D057507: Mice, 129 Strain (Publication, NCBO Annotator)
  • GO:0046903: secretion (Publication, NCBO Annotator)
  • D010949: Plasma (Publication, NCBO Annotator)
  • D001053: Apolipoproteins (Publication, NCBO Annotator)
  • D002894: Chromosomes, Human, Pair 4 (Publication, NCBO Annotator)
  • D002896: Chromosomes, Human, Pair 6 (Publication, NCBO Annotator)
  • D012380: Role (Publication, NCBO Annotator)
  • D016017: Odds Ratio (Publication, NCBO Annotator)
  • D006321: Heart (Publication, NCBO Annotator)
  • D005190: Family (Publication, NCBO Annotator)
  • D001055: Apolipoproteins B (Publication, NCBO Annotator)
  • D003327: Coronary Disease (Publication, NCBO Annotator)
  • D012926: Social Control, Formal (Publication, NCBO Annotator)
  • MA:0002501: plasma (Publication, NCBO Annotator)
  • D053299: Apolipoprotein B-100 (Publication, NCBO Annotator)
  • MA:0000072: heart (Publication, NCBO Annotator)
  • D006331: Heart Diseases (Publication, NCBO Annotator)
  • D006995: Hypobetalipoproteinemias (Publication, NCBO Annotator)

2 GeneSets from this Publication:

Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
Expand Tier II Mouse 499 Genes GS136418: plasma apolipoprotein B (human) regulator 1 (Pabr1, Published QTL Chr 6)
Expand Tier II Mouse 272 Genes GS136419: plasma apolipoprotein B (human) regulator 2 (Pabr2, Published QTL Chr 4)