Genetic Analysis of "Metabolic Syndrome" in the Spontaneously Hypertensive Rat

Abstract

In the current review, we summarize results of genetic analyses of "metabolic syndrome" in the spontaneously hypertensive rat (SHR). These results include (1) linkage analyses in the HXB/BXH recombinant inbred (RI) strains derived from SHR and Brown Norway (BN-Lx) strains which revealed quantitative trait loci (QTL) for hemodynamic and metabolic traits on several chromosomes, (2) genetic isolation of these putative QTL within differential chromosome segments of SHR.BN congenic strains, (3) detailed mapping of these QTL within limited chromosome segments of SHR.BN congenic sublines, (4) sequencing of selected positional candidate genes which revealed important mutations in the Cd36 and Srebp1 SHR genes, (5) functional tests of these candidate genes in SHR transgenic lines, and (6) integrated gene expression profiling and linkage mapping in RI strains which will be used to identify co-regulated genes and to determine co-segregation of transcriptional profiles with physiological and pathophysiological phenotypes.