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J Appl Physiol 94: 2510-2522, 2003; doi:10.1152/japplphysiol.00064.2003
8750-7587/03 $5.00
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Vol. 94, Issue 6, 2510-2522, June 2003

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

Morton P. Printz1, Martin Jirout1,2, Rebecca Jaworski1, Adamu Alemayehu1, and Vladimir Kren2,3

1 Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0636; 2 Institute of Biology and Medical Genetics, Charles University, Prague 128 00; and 3 Institute of Physiology, Czech Academy of Sciences, Prague, The Czech Republic 142 20

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. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.

quantitative trait loci; gene map; arterial pressure; heart rate; stress response; malformation phenotype


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