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doi:10.1534/genetics.106.057455
A more recent version of this article appeared on June 1, 2006.
REGULAR RESEARCH PAPERS |
Complex Inheritance of the 5-Lipoxygenase Locus Influencing Atherosclerosis in Mice
Anatole Ghazalpour 1, Xuping Wang 1, Aldons J Lusis 1 and Margarete Mehrabian 1*
1 UCLA
* To whom correspondence should be addressed. E-mail: mehrabi.m{at}gmail.com.
Submitted on February 21, 2006
Revised on March 24, 2006
Accepted on 7 April 2006
We previously mapped a locus on chromosome 6 with a large effect (LOD>6) on aortic lesion size in a (C57BL/6JxCAST/Ei) F2 cross and identified arachidonate 5-lipoxygenase (5LO) as a candidate gene in this region. Subsequent studies with the 5LO knock-out model showed effects on atherosclerosis and aortic aneurysms. We now report detailed genetic analysis of the chromosome 6 locus. We created a panel of overlapping and reciprocal subcongenic lines from the B6.CAST Ldlr-/- chromosome 6 congenic strain (CON6.Ldlr-/-) and analyzed aortic lesion size in different subcongenic lines. Our results revealed that there are at least two subregions which affect the size of aortic lesions independent of 5LO. We also showed that homozygote 5LO null mice develop smaller atherosclerotic lesions. We conclude that the relation between the mouse chromosome 6 locus and atherosclerosis is complex and is due to at least two genes with large effects within this region. This complexity should be considered when interpreting results of knock-out studies.
Key Words: 5-lipoxygenase, aneurysm, atherosclerosis, fine mapping, subcongenics
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