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Journal of Lipid Research, Vol. 48, 1724-1734, August 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Mapping genetic loci that regulate lipid levels in a NZB/B1NJxRF/J intercross and a combined intercross involving NZB/B1NJ, RF/J, MRL/MpJ, and SJL/J mouse strains

Jon E. Wergedal^*,, Cheryl L. Ackert-Bicknell, Wesley G. Beamer, Subburaman Mohan^*,, David J. Baylink^* and Apurva K. Srivastava^1,*,

^* Musculoskeletal Disease Center, Loma Linda VA Health Care Systems, Loma Linda, CA
Department of Medicine, Loma Linda University, Loma Linda, CA
Jackson Laboratory, Bar Harbor, ME

Published, JLR Papers in Press, May 13, 2007.

¹ To whom correspondence should be addressed. e-mail: apurva.srivastava{at}med.va.gov

The NZB/B1NJ (NZB) mouse strain exhibits high cholesterol and HDL levels in blood compared with several other strains of mice. To study the genetic regulation of blood lipid levels, we performed a genome-wide linkage analysis in 542 chow-fed F2 female mice from an NZBxRF/J (RF) intercross and in a combined data set that included NZBxRF and MRL/MpJxSJL/J intercrosses. In the NZBxRF F2 mice, the cholesterol and HDL concentrations were influenced by quantitative trait loci (QTL) on chromosome (Chr) 5 [logarithm of odds (LOD) 17–19; D5Mit10] that was in the region identified earlier in crosses involving NZB mice, but two QTLs on Chr 12 (LOD 4.7; D12Mit182) and Chr 19 (LOD 5.7; D19Mit1) were specific to the NZBxRF intercross. Triglyceride levels were affected by two novel QTLs at D12Mit182 (LOD 8.7) and D15Mit13 (LOD 3.5). The combined-cross linkage analysis (1,054 mice, 231 markers) 1) identified four shared QTLs (Chrs 5, 7, 14, and 17) that were not detected in one of the parental crosses and 2) improved the resolution of two shared QTLs. In summary, we report additional loci regulating lipid levels in NZB mice that had not been identified earlier in crosses involving the NZB strain of mice. The identification of shared loci from multiple crosses increases confidence toward finding the QTL gene.

Supplementary key words high density lipoprotein cholesterol • cholesterol • triglyceride • quantitative trait loci • combined-cross linkage analysis

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