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Effects of chromosome 17 on features of the metabolic syndrome in the Lyon hypertensive rat

¹ Département de Physiologie et Pharmacologie Clinique, Institut des Sciences Pharmaceutiques et Biologiques, Université Lyon 1, Lyon, France
² Human and Molecular Genetics Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
³ Max Delbruck Center for Molecular Medicine, Berlin-Buch, Germany

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 of the metabolic syndrome, having high body weight, plasma cholesterol, and triglycerides, increased insulin-to-glucose ratio, and salt-sensitive hypertension. Previous genetic studies in LH/Mav rats 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 rat, we generated a consomic strain (LH-17^BN) by substituting LH RNO17 with that of the sequenced Brown Norway (BN/NHsdMcwi) rat. Male LH and BN rats and LH-17^BN rats were characterized for blood pressure and metabolic and morphological parameters. Similar to the protective effect of LN alleles, the LH-17^BN rat also showed decreased body weight, triglycerides, and blood pressure; however, there was no significant difference in cholesterol or insulin-to-glucose ratio. 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 and morphological and metabolic traits on this chromosome.

consomic; hypertension