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Physiol. Genomics 17: 38-47, 2004. First published January 6, 2004; doi:10.1152/physiolgenomics.00043.2003
1094-8341/04 $5.00
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Received 28 March 2003; accepted in final form 23 December 2003.
Physiological Genomics 17:38-47 (2004)
1094-8341/04 $5.00 © 2004 American Physiological Society

Rat model of familial combined hyperlipidemia as a result of comparative mapping

Takahiro Ueno 1, Johanne Tremblay 1, Jaroslav Kunes 2, Josef Zicha 2, Zdenka Dobesova 2, Zdenka Pausova 1, Alan Y. Deng 1, Yu-Lin Sun 1, Howard J. Jacob 3 and Pavel Hamet 1

1 Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, Quebec, Canada
2 Institute of Physiology, Czech Academy of Sciences, Czech Republic
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Total genome scan was carried out in 266 F2 intercrosses from the Prague hypertriglyceridemic (HTG) rat that shares several clinical characteristics with human metabolic syndrome. Two loci for plasma triglycerides (TG) were localized on chromosome 2 (Chr 2) (LOD 4.4, 3.2). The first locus overlapped with the rat syntenic region of the human locus for the metabolic syndrome and for small, dense LDL, while the second overlapped with the syntenic region of another locus for small, dense LDL in humans by the comparative mapping approach. Loci for TG on rat Chr 13 (LOD 3.3) and Chr 1 (LOD 2.7) overlapped with the syntenic region of loci for human familial combined hyperlipidemia (FCHL) in Finnish and Dutch populations, respectively. The concordances of loci for TG localized in this study with previously reported loci for FCHL and its related phenotypes are underlying the generalized importance of these loci in dyslipidemia. These data suggest the close relationship between dyslipidemia in HTG rats and human FCHL, establishing a novel animal model for exploration of pathophysiology and therapy based on genomic determinants.

Prague hypertriglyceridemic rat; quantitative trait locus; triglycerides; cholesterol; metabolic syndrome




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