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Quantitative Analysis and Characterization of Atherosclerotic Lesions in the Murine Aortic Sinus
Published on: December 7, 2013
Genetic modifiers of atherosclerosis in mice
J D Smith1, H M Dansky, J L Breslow
1The Rockefeller University, New York, New York 10021, USA. smithj@mail.rockefeller.edu
Annals of the New York Academy of Sciences
|January 25, 2002
Summary
Researchers identified genetic factors influencing atherosclerosis susceptibility using a mouse model. Gene mutations in MCSF and VCAM-1 reduced atherosclerosis, and genetic mapping revealed key susceptibility loci.
Area of Science:
- Genetics
- Cardiovascular Research
- Animal Models
Background:
- Atherosclerosis has a complex genetic basis, making human gene identification challenging.
- The apolipoprotein E (apoE)-deficient mouse serves as a valuable model for studying atherosclerosis genetics.
Purpose of the Study:
- To investigate the impact of specific gene mutations on atherosclerosis development.
- To identify novel genetic loci associated with atherosclerosis susceptibility using quantitative trait locus mapping.
Main Methods:
- Testing the effects of mutations in the MCSF and VCAM-1 genes on atherosclerosis.
- Establishing apoE-deficiency in different inbred mouse strains (C57BL/6 and FVB/N) through backbreeding.
- Performing quantitative trait locus (QTL) mapping on F2 intercross cohorts.
Main Results:
- Mutations in MCSF and VCAM-1 genes resulted in gene dosage-dependent reductions in atherosclerosis.
- Significant differences in lesion size were observed between C57BL/6 (larger lesions) and FVB/N (smaller lesions) apoE-deficient mice.
- QTL analysis identified atherosclerosis susceptibility loci on chromosomes 10, 14, and 19.
Conclusions:
- Candidate gene mutations can modulate atherosclerosis, highlighting their potential roles.
- Genetic background significantly influences atherosclerosis severity in apoE-deficient mice.
- Novel genetic loci contributing to atherosclerosis susceptibility have been mapped, providing targets for further research.
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