Physiol. Genomics AJP: Lung Cellular and Molecular Physiology
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Physiol. Genomics (June 13, 2006). doi:10.1152/physiolgenomics.00004.2006
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Submitted on January 9, 2006
Accepted on June 8, 2006

CONSOMIC STRATEGIES TO LOCALIZE GENOMIC REGIONS RELATED TO VASCULAR REACTIVITY IN THE DAHL SALT SENSITIVE RAT

Mary Pat Kunert1*, Ines Drenjancevic-Peric2, Melinda R Dwinell2, Julian H Lombard2, Allen W. Cowley Jr.3, Andrew S Greene4, Anne E Kwitek4, and Howard J Jacob5

1 Nursing, University of Wisconsin-Milwaukee, Milwaukee, United States; Physiology, Medical College of Wisconsin, Milwaukee, United States
2 Physiology, Medical College of Wisconsin, Milwaukee, United States
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
4 Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
5 Human Molecular and Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

* To whom correspondence should be addressed. E-mail: mpkunert{at}uwm.edu.

Chromosomal substitution strains afford the opportunity to discover regions of the rat genome that contain genes related to cardiovascular traits with the long range goal of linking these genes to physiological function. PhysGen (Programs for Genomic Applications) created a consomic panel of rats derived from the introgression of a single chromosome (≥95% of the BN chromosome, one at a time) of the Brown Norway (BN/NHsdMcwi) rat onto the homogeneous genetic background of the Dahl salt sensitive rat (SS/JrHsdMcwi). For three weeks prior to the experiment, the rats were maintained on a low salt diet (0.4% NaCl). The dose response of aortic rings from each strain of rat to phenylephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and three different levels of tissue bath hypoxia (10, 5 and 0% O2) were measured and compared to the parental SS rat. In order to maximize the possibility that differences among the strains would become apparent, each strain of rat including the parental SS and BN was also studied after being maintained on a high salt diet (4.0% NaCl) for three weeks. If the response of the aortic ring from a consomic strain to these vasoactive substances was different than that from the SS parental strain it was concluded that the introgressed chromosome contained a gene or genes that contributed to that difference. Because the BN chromosome is removed from its native background and the SS rat loses a native chromosome it is also necessary to consider the contribution of changes in gene-to-gene interaction.




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