Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans.
Document Type
Article
Publication Date
2004
Keywords
Chromosome-Mapping, Chromosomes-Mammalian, Genetic-Predisposition-to-Disease, Humans, Lod-Score, Mice, Mice-Inbred-Strains, Quantitative-Trait-Loci
First Page
443
Last Page
450
JAX Source
Atherosclerosis 2004 Dec; 177(2):443-50.
Abstract
A previous study revealed that the difference in susceptibility to atherosclerotic lesions between inbred mouse strains SM/J and NZB/BlNJ was determined by one major locus (Ath8). In this study a (SM/J x NZB/BlNJ) F(1) x SM/J backcross localized Ath8 by quantitative trait locus mapping to chromosome 4 with a suggestive LOD score of 2.7. This quantitative trait locus (QTL) was confirmed using an (SM/J x NZB/BlNJ) intercross; Ath8 mapped to a 23cM region with a significant LOD score of 3.6. The genes for toll-like receptor 4 (T1r4), arachidonic acid epoxygenase (Cyp2j5), and angiopoietin-like protein 3 (Angptl3) map to this region. These candidate genes were analyzed for expression and sequence differences in the mouse and for associations with cardiovascular traits in human. Sequence analysis of Angptl3 shows a base pair substitution in SM, the susceptible strain, giving rise to an amino acid change in the fibrinogen homology domain of the protein. We found a significant association between ANGPTL3 and atherosclerotic lesions (P < 0.05) in human. These results suggest that Angptl3 is involved in atherosclerosis susceptibility in both mouse and human.
Recommended Citation
Korstanje R,
Eriksson P,
Samnegard A,
Olsson PG,
Forsman SK,
Sen S,
Churchill GA,
Rollins J,
Harris S,
Hamsten A,
Paigen B.
Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans. Atherosclerosis 2004 Dec; 177(2):443-50.