J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on August 1, 2007

Papers In Press, published online ahead of print May 13, 2007
J. Lipid Res., doi:10.1194/jlr.M700015-JLR200
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Submitted on January 10, 2007
Revised on April 12, 2007
Accepted on May 12, 2007

Mapping genetic loci that regulate lipid levels in a NZB/B1NJ×RF/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

Musculoskeletal Disease Center, Loma Linda VA Healthcare Systems, Loma Linda, CA 92357

Corresponding Author: Apurva.Srivastava{at}med.va.gov

The NZB/BlNJ (NZB) mouse strain exhibits high cholesterol and HDL levels in blood as compared to several other strains of mice. To study genetic regulation of blood lipid levels, we performed a genome-wide linkage analysis in 542 chow fed F2 female mice from an NZB/B1NJRF/J intercross and in a combined data set which included NZB/B1NJRF/J and MRL/MpJSJL/J intercrosses. In the NZB/B1NJRF/J F2 mice, the cholesterol and HDL concentrations were influenced by quantitative trait loci (QTL) on chromosome (Chr) 5 (LOD 17-19, D5Mit10) that was in the region identified earlier in crosses involving NZB/B1NJ mice, but two QTLs on Chr 12 (LOD 4.7, D12Mit182) and Chr 19 (LOD 5.7, D19Mit1) were specific to the NZB/B1NJRF/J intercross. Triglyceride levels were affected by two novel QTL at D12Mit182 (LOD 8.7) and D15Mit13 (LOD 3.5). The combined-cross linkage analysis (1054 mice, 231 markers): 1) identified four shared QTLs (Chrs 5, 7, 14, 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/B1NJ mice that had not been identified earlier in crosses involving the NZB/B1NJ strain of mice. The identification of shared loci from multiple-crosses increases the confidence towards finding the QTL gene.


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I. M. Stylianou, S. R. Langley, K. Walsh, Y. Chen, C. Revenu, and B. Paigen
Differences in DBA/1J and DBA/2J reveal lipid QTL genes
J. Lipid Res., November 1, 2008; 49(11): 2402 - 2413.
[Abstract] [Full Text] [PDF]


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