MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension.

Hypertension is a common hereditary syndrome with unclear pathogenesis. Chromogranin A (Chga), which catalyzes formation and cargo storage of regulated secretory granules in neuroendocrine cells, contributes to blood pressure homeostasis centrally and peripherally. Elevated Chga occurs in spontaneously hypertensive rat (SHR) adrenal glands and plasma, but central expression is unexplored.

Identification of quantitative trait Loci for anxiety and locomotion phenotypes in rat recombinant inbred strains.

Anxiety disorders are phenotypically complex and may involve multiple genetic influences on many neurotransmitter systems. Rodent tests used to investigate genetic influences on anxiety-like phenotypes have face and predictive validity as models for anxiety in humans. If multiple genes contribute additively to a trait, the trait will be continuously distributed and be amenable to detection of associations between allelic variation at specific chromosomal loci and the phenotypes being studied via quantitative trait loci (QTL) mapping.

A new framework marker-based linkage map and SDPs for the rat HXB/BXH strain set.

A new contiguous genetic linkage map of the HXB/BXH set of rat recombinant inbred (RI) strains was constructed to enhance QTL mapping power and precision, and thereby make the RI strain set a better genomics resource. The HXB/BXH rat RI strains were developed from a cross between the hypertensive SHR/OlaIpcv and normotensive BN- Lx/Cub rat strains and have been shown useful for identifying quantitative trait loci (QTL) for a variety of cardiovascular, metabolic, and behavioral phenotypes. In the current analysis, the DNAs from 31 existing strains, 1 substrain, and 4 extinct strains were genotyped for a selection of polymorphic microsatellite marker loci, predominantly polymorphic framework markers from high-density integrated rat genome maps.

Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics.

This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy.

Heart rate and blood pressure quantitative trait loci for the airpuff startle reaction.

The airpuff startle reaction is a probe of sensori-autonomic processing and is useful for studies of genetic control of stress-induced cardiovascular activity. Using a Wistar-Kyoto-Spontaneously Hypertensive Rat F2 cross, we reported an airpuff-elicited strain-dependent and trial-dependent bradycardia, the absence of which cosegregated with hypertension. Here, we use the mapping power of the HXB-BXH recombinant inbred rat strains (n=23) to locate quantitative trait loci (QTL) for this and associated cardiovascular phenotypes.