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POSTER 29 - LOCALIZATION OF ATH8, A QUANTITATIVE TRAIT LOCUS FOR LESION SIZE IN THE MOUSE
Dr Ron Korstanje
The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609
USA
Co-Authors: 1)Pitman, WA, 1)Sen, S, 1)Churchill, GA, 2)Harris, S, 1)Paigen, B
InstitutionsS: 1)The Jackson Laboratory, 2)Glaxo Wellcome
A previous study revealed that the difference in susceptibility to atherosclerotic lesions between inbred strains of mice SM/J and NZB/BlNJ was determined by one major gene (Ath8). In this study a small (SM/J x NZB/BlNJ) F1 x SM/J backcross localized this gene by quantitative trait locus mapping to chromosome 4 in a genome wide scan with a LOD score of 2.7. Lesion size was not correlated with total cholesterol or HDL cholesterol. The suggestive QTL was confirmed using an (SM/J x NZB/B1NJ) intercross with 515 F2 animals; Ath8 mapped to a 20 cM region between D4Mit214 and D4Mit306 with a LOD score of 3.6. This region has a 3.8 cM overlap with the 7.2 cM region that was found using a recombinant inbred segregation test (RIST). In addition, a fragment containing the gene for carnitine palmitoyl transferase II (Cpt2), a possible candidate gene, was mapped to the RIST region using the Jackson Laboratory DNA panel from a (C57BL/6J x SPRET/Ei) SPRET/Ei backcross. The identification of the gene underlying the Ath8 phenotype will lead to further insights into the atherosclerotic process.
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