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Use of Rat Genomics for Investigating the Metabolic Syndrome

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Rat Genomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 597))

Abstract

The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and accompanying metabolic disturbances. In this model, the use of whole genome sequencing and gene expression profiling techniques, linkage and correlation analyses in recombinant inbred strains, and in vitro and in vivo functional studies in congenic and transgenic lines has recently enabled molecular identification of quantitative trait loci (QTLs) relevant to the metabolic syndrome: (1) a deletion variant in Cd36 (fatty acid translocase) responsible for QTLs on chromosome 4 associated with dyslipidemia, insulin resistance and hypertension, (2) mutated Srebf1 (sterol regulatory element binding factor 1) as a QTL on chromosome 10 influencing dietary-induced changes in hepatic cholesterol levels, and (3) Ogn (osteoglycin) as a QTL on chromosome 17 associated with left ventricular hypertrophy. In addition, selective replacement of the mitochondrial genome of the SHR with the mitochondrial genome of the Brown Norway rat influenced several major metabolic risk factors for type 2 diabetes and provided evidence that spontaneous variation in the mitochondrial genome per se can promote systemic metabolic disturbances relevant to the pathogenesis of metabolic syndrome. Owing to recent progress in the development of rat genomic resources, the pace of QTL identification and discovery of new disease mechanisms can be expected to accelerate in the near future.

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Acknowledgments

This work was supported by grants 1P05ME791 and 1M6837805002 from the Ministry of Education of the Czech Republic, grants 301/06/0028 and 301/08/0166 from the Grant Agency of the Czech Republic, grant IAA500110604 from the Grant Agency of the Academy of Sciences of the Czech Republic, and by the European Commission within the Sixth Framework Programme through the Integrated Project EURATools (contract no. LSHG-CT-2005-019015). M.P. is an international research scholar of the Howard Hughes Medical Institute.

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  1. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

    Michal Pravenec

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  1. Michal Pravenec
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Correspondence to Michal Pravenec .

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Editors and Affiliations

  1. ITERT-INSERM U643, CHU de Nantes, bd. Jean Monnet 30, Nantes, 44093, France

    Ignacio Anegon

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Pravenec, M. (2010). Use of Rat Genomics for Investigating the Metabolic Syndrome. In: Anegon, I. (eds) Rat Genomics. Methods in Molecular Biology, vol 597. Humana Press. https://doi.org/10.1007/978-1-60327-389-3_28

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  • DOI: https://doi.org/10.1007/978-1-60327-389-3_28

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-388-6

  • Online ISBN: 978-1-60327-389-3

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