Submitted on March 4, 2006
Accepted on June 23, 2006
Novel double-congenic strain reveals effects of spontaneously hypertensive rat chromosome 2 on specific lipoprotein subfractions and adiposity
Ondrej Seda1, Lucie Sedova2, Frantisek Liska2, Drahomira Krenova2, Vratislav Prejzek2, Ludmila Kazdova3, Johanne Tremblay4, Pavel Hamet4, and Vladimir Kren2*
1 Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles Uiversity in Prague, Prague, Czech Republic; Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Laboratory of Molecular Medicine, Research Centre CHUM, Montreal, Canada
2 Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles Uiversity in Prague, Prague, Czech Republic
3 Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
4 Laboratory of Molecular Medicine, Research Centre CHUM, Montreal, Canada
* To whom correspondence should be addressed. E-mail: vladimir.kren{at}lf1.cuni.cz.
We have developed new, double-congenic rat strain BN-Lx.SHR2, which carries two distinct segments of chromosome 2 introgressed from the spontaneously hypertensive rat strain (SHR) into the genetic background of congenic strain BN-Lx, which was previously shown to express variety of metabolic syndrome features. In 16-week-old male rats of BN-Lx and BN-Lx.SHR2 strains, we compared their glucose tolerance, triacylglycerol and cholesterol concentrations in 20 lipoprotein subfractions and the lipoprotein particle sizes under conditions of feeding standard and high-sucrose diets. Introgression of two distinct SHR-derived chromosome 2 segments resulted in decrease of adiposity together with aggravation of glucose intolerance in the double-congenic strain. The BN-Lx.SHR2 rats were more sensitive to sucrose-induced rise in triacylglycerolemia. Although the total cholesterol concentrations of the two strains were comparable after standard diet and even lower in BN-Lx.SHR2 after sucrose feeding, detailed analysis revealed that under both dietary conditions, the double-congenic strain had significantly higher cholesterol concentrations in LDL fractions and lower in HDL fractions. We established new inbred model showing dyslipidemia and mild glucose intolerance without obesity, attributable to specific genomic regions. For the first time, the chromosome 2 segments of SHR origin are shown to influence other than blood pressure-related features of metabolic syndrome or to be involved in relevant nutrigenomic interactions.
