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Dissection of multigenic obesity traits in congenic mouse strains

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Abstract

Previous quantitative trait locus mapping (QTL) identified multigenic obesity (MOB) loci on mouse Chromosome (Chr) 2 that influence the interrelated phenotypes of obesity, insulin resistance, and dyslipidemia. To better localize and characterize the MOB locus, three congenic mouse strains were created. Overlapping genomic intervals from the lean CAST/Ei (CAST) strain were introgressed onto an obesity-susceptible C57BL/6 (BL6) background to create proximal (15 Mb–73 Mb), middle (63 Mb–165 Mb), and distal (83 Mb–182 Mb) congenic strains. The congenic strains showed differences in obesity, insulin, and lipid traits consistent with the original QTL analysis for the locus. Importantly, characterization of the MOB congenics localized the effects of genes that underlie obesity-related traits to an introgressed interval (73–83 Mb) unique to the middle MOB congenic. Conversely, significant differences between the lipid and insulin profiles of the middle and distal MOB congenics implicated the presence of at least two genes that underlie these traits. When fed an atherogenic diet, several traits associated with metabolic syndrome were observed in the distal MOB congenic, while alterations in plasma lipoproteins were observed in the middle MOB congenic strain.

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Acknowledgements

We acknowledge the valuable contributions of Andrea Terada and Craig Crockett for assistance in animal husbandry and characterization of the MOB congenic strains. This work was supported by a National Science Foundation fellowship for Daria Estrada-Smith from 1999 to 2002 and National Institutes of Health grants HL60030, HL28481, and CA 42710.

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Authors and Affiliations

  1. Department of Human Genetics, Gonda/Goldschmeid Center for Neuroscience and Human Genetics Research, 695 Charles E. Young Dr. South, Room 6524, Los Angeles, CA 90095-7088, USA

    Daria Estrada-Smith & Aldons J. Lusis

  2. Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA

    Lawrence W. Castellani, Howard Wong, Ping-Zi Wen, Aileen Chui, Aldons J. Lusis & Richard C. Davis

  3. Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA

    Aldons J. Lusis

Authors
  1. Daria Estrada-Smith
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  2. Lawrence W. Castellani
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  3. Howard Wong
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  4. Ping-Zi Wen
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  6. Aldons J. Lusis
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  7. Richard C. Davis
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Correspondence to Daria Estrada-Smith.

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Estrada-Smith, D., Castellani, L.W., Wong, H. et al. Dissection of multigenic obesity traits in congenic mouse strains . Mamm Genome 15, 14–22 (2004). https://doi.org/10.1007/s00335-003-2294-8

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  • DOI: https://doi.org/10.1007/s00335-003-2294-8

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