Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans

Ron Korstanje, Per Eriksson, Ann Samnegård, Per G. Olsson, Kristina Forsman-Semb, Saunak Sen, Gary A. Churchill, Jarod Rollins, Stephen Harris, Anders Hamsten, Beverly Paigen

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 × NZB/BlNJ) F 1 × 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 × NZB/BlNJ) intercross; Ath8 mapped to a 23 cM 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.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalAtherosclerosis
Volume177
Issue number2
DOIs
StatePublished - Dec 1 2004

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Angiopoietins
Atherosclerosis
Quantitative Trait Loci
Genes
Chromosomes, Human, Pair 4
Toll-Like Receptor 4
Inbred Strains Mice
Proteins
Base Pairing
Fibrinogen
Sequence Analysis
Amino Acids

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans. / Korstanje, Ron; Eriksson, Per; Samnegård, Ann; Olsson, Per G.; Forsman-Semb, Kristina; Sen, Saunak; Churchill, Gary A.; Rollins, Jarod; Harris, Stephen; Hamsten, Anders; Paigen, Beverly.

In: Atherosclerosis, Vol. 177, No. 2, 01.12.2004, p. 443-450.

Research output: Contribution to journalArticle

Korstanje, R, Eriksson, P, Samnegård, A, Olsson, PG, Forsman-Semb, K, Sen, S, Churchill, GA, Rollins, J, Harris, S, Hamsten, A & Paigen, B 2004, 'Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans', Atherosclerosis, vol. 177, no. 2, pp. 443-450. https://doi.org/10.1016/j.atherosclerosis.2004.08.006
Korstanje, Ron ; Eriksson, Per ; Samnegård, Ann ; Olsson, Per G. ; Forsman-Semb, Kristina ; Sen, Saunak ; Churchill, Gary A. ; Rollins, Jarod ; Harris, Stephen ; Hamsten, Anders ; Paigen, Beverly. / Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans. In: Atherosclerosis. 2004 ; Vol. 177, No. 2. pp. 443-450.
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