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Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains

¹Department of Physiology, ²Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 12 October 2004 ; accepted in final form 14 December 2004

To understand the genetic basis of pathways involved in the control of breathing, a large scale, high-throughput study using chromosomal substitution strains of rats is underway. Eight new consomic rat stains (SS-2^BN, SS-4^BN, SS-6^BN, SS-7^BN, SS-8^BN, SS-11^BN, SS-12^BN, SS-14^BN, SS-Y^BN), containing one homozygous BN/NHsdMcwi (BN) chromosome on a background of SS/JrHsdMcwi (SS), were created by PhysGen (http://pga.mcw.edu) Program for Genomic Applications. Male and female rats were studied using standard plethysmography under control conditions and during acute hypoxia (inspired oxygen fraction = 0.12) and hypercapnia (inspired CO₂ fraction = 0.07). The rats were also studied during treadmill exercise. Both male and female BN rats had a significantly lower ventilatory response during 7% CO₂ compared with SS rats of the same gender. SS-6^BN female rats had a significantly reduced ventilatory response, similar to BN rats due primarily to a reduced tidal volume. Male SS-6^BN rats had a significantly reduced tidal volume response to hypercapnia but a slightly increased frequency response during hypercapnia. Gene(s) on the Y chromosome may play a role in this increased frequency response in the male rats because the SS-Y^BN hypercapnic ventilatory response involves a significantly increased frequency response. Several chromosomal substitutions slightly altered the ventilatory responses to hypoxia and exercise. However, genes on chromosomes 6 and Y of those studied are of primary importance in aspects of ventilatory control currently studied.

control of breathing; chromosomal substitution; hypoxia; hypercapnia; exercise

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