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Genetic loci for diet-induced atherosclerotic lesions and plasma lipids in mice

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Abstract

Genetic factors independent of those affecting plasma lipid levels are a major contributor to risk for atherosclerosis in humans, yet the basis for these is poorly understood. This study examined plasma lipids and diet-induced atherosclerosis in 16-month-old female mice of strains C56BL/6J and DBA/2J. Mice of the parental strains, from recombinant inbred strains derived from these (BXD RI), and F2 progeny were fed an atherogenic diet for 16 weeks, beginning at 1 year of age. This induced atherosclerotic lesion formation in both parental strains, accompanied by increased plasma LDL levels. However, individual BXD RI strains and the BXD F2 mice demonstrated a range of atherosclerotic lesion formation that was not or at best weakly correlated with plasma lipid levels. Quantitative trait locus (QTL) analysis of the BXD F2 mice identified a locus with significant linkage (lod 4.5) for aortic lesion size on Chromosome (Chr) 10 that was independent of plasma lipids. Other loci with suggestive or significant linkage for various plasma lipid measures were identified on Chr 2, 3, 4, 5, 6, 7, 11, and 17. In this intercross, the genes primarily influencing atherosclerosis are distinct from those controlling plasma lipid levels.

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Acknowledgements

The assistance of Larry Castellani, Sharda Charungundla, Marjon Jahromi, Kathy Salcedo, and Yishou Shi is gratefully acknowledged. This work was supported by NIH grant HL30568 (A.J. Lusis and T.A. Drake) and by the Laubisch Fund, UCLA.

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Authors and Affiliations

  1. Department of Microbiology, Immunology and Molecular Genetics, University of California-Los Angeles, Los Angeles, California 90095, USA

    Veronica V. Colinayo, Kelly L. Krass & Aldons J. Lusis

  2. Department of Pathology and Laboratory Medicine, University of California-Los Angeles, Los Angeles, California 90095, USA

    Jian-Hua Qiao & Thomas A. Drake

  3. Department of Medicine, University of California-Los Angeles, Los Angeles, California 90095, USA

    Xuping Wang & Aldons J. Lusis

  4. Department of Human Genetics, University of California, Los Angeles, California 90095, USA

    Aldons J. Lusis

  5. Rosetta Inpharmatics, Kirkland, LCC, Washington 98034, USA

    Eric Schadt

Authors
  1. Veronica V. Colinayo
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  2. Jian-Hua Qiao
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  3. Xuping Wang
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  4. Kelly L. Krass
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  5. Eric Schadt
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  6. Aldons J. Lusis
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  7. Thomas A. Drake
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Corresponding author

Correspondence to Thomas A. Drake.

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Colinayo, V.V., Qiao, JH., Wang, X. et al. Genetic loci for diet-induced atherosclerotic lesions and plasma lipids in mice . Mamm Genome 14, 464–471 (2003). https://doi.org/10.1007/s00335-002-2187-2

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  • DOI: https://doi.org/10.1007/s00335-002-2187-2

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