Submitted on November 7, 2007
Accepted on February 9, 2008
THE EFFECTS OF CHROMOSOME 17 ON FEATURES OF THE METABOLIC SYNDROME IN THE LYON HYPERTENSIVE (LH) RAT
Sophie Gilibert1, Anne E Kwitek2*, Norbert Hubner3, Michael Tschannen4, Howard J Jacob4, Jean Sassard5, and Alain P Bataillard6
1 Departement de Physiologie et Pharmacologie Clinique, Universite de Lyon, Lyon, France
2 Human Molecular and Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
3 Max Delbrueck Center for Molecular Medicine, Berlin-Buch, Germany
4 Human Molecular and Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
5 Departement de Physiologie et Pharmacologie Clinique, Faculte de Pharmacie, CNRS ESA 50148 Av Rockefeller, Lyon, France; Departement de Physiologie et Pharmacologie Clinique, Universite de Lyon, Lyon, France
6 Physiology and Clinical Pharmacology, Faculty of Pharmacy, Lyon, France; Departement de Physiologie et Pharmacologie Clinique, Universite de Lyon, Lyon, France
* To whom correspondence should be addressed. E-mail: anne-kwitek{at}uiowa.edu.
The metabolic syndrome (involving obesity, hypertension, dyslipidemia, insulin resistance, and a proinflammatory/prethrombotic state), is a major risk factor for cardiovascular disease. Its incidence continues to rise, in part because of the epidemic increase in obesity. The Lyon Hypertensive (LH) rat is a model for hypertension and several other features for the metabolic syndrome, having high body weight, plasma cholesterol and triglycerides, increased insulin/glucose ratio, and salt-sensitive hypertension. Previous genetic studies in LH/Mav and a normotensive control (LN/Mav) identified Quantitative Trait Loci (QTLs) on rat chromosome (RNO) 17 for multiple features of the metabolic syndrome. To further evaluate the role of RNO17 in the LH, we generated a consomic strain (LH-17BN) by substituting LH RNO17 with that of the sequenced Brown Norway (BN/NHsdMcwi) rat. Male LH and BN, and LH-17BN rats were characterized for blood pressure, metabolic and morphological parameters. Similar to the protective effect of LN alleles, the LH-17BN also shows decreased body weight, triglycerides, and blood pressure; however there was no significant difference in cholesterol or insulin/glucose ratios. Therefore, the substitution of the LH chromosome 17 is sufficient to recapitulate some, but not all, of the traits previously mapped to this chromosome. This could be due to the lack of a susceptible LH genome background or due to the introgression of chromosome 17 from another strain. Regardless, this study provides a single-chromosome genetic model for further dissection of blood pressure, morphological, and metabolic traits on this chromosome.
