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Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic
M R Dwinell1, H V Forster, J Petersen
1Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. mrdwinel@mcw.edu
Journal of Applied Physiology (Bethesda, Md. : 1985)
|January 22, 2005
Summary
Researchers identified specific rat chromosomes influencing breathing control. Genes on chromosomes 6 and Y significantly impact ventilatory responses to carbon dioxide, hypoxia, and exercise.
Area of Science:
- Physiology
- Genetics
- Respiratory Control
Background:
- Understanding the genetic underpinnings of respiratory control is crucial for addressing breathing disorders.
- Chromosomal Substitution Strain (CSS) rats offer a powerful tool for mapping quantitative trait loci (QTLs) influencing complex physiological traits.
Purpose of the Study:
- To investigate the genetic basis of ventilatory control using novel consomic rat strains.
- To identify specific chromosomes that harbor genes regulating respiratory responses to hypoxia, hypercapnia, and exercise.
Main Methods:
- Creation of eight new consomic rat strains (SS-2(BN) to SS-Y(BN)) by transferring Brown Norway (BN) chromosomes onto a Sprague-Dawley (SS) genetic background.
- Assessment of ventilatory responses in male and female consomic rats under normoxia, acute hypoxia (12% O2), and hypercapnia (7% CO2) using plethysmography.
- Evaluation of respiratory parameters during treadmill exercise.
Main Results:
- BN rats exhibited significantly lower ventilatory responses to hypercapnia compared to SS rats.
- SS-6(BN) female rats showed a reduced ventilatory response to hypercapnia, primarily due to decreased tidal volume, mirroring BN rat responses.
- SS-Y(BN) male rats displayed an increased breathing frequency response to hypercapnia, suggesting a role for Y-chromosome genes.
Conclusions:
- Genes located on rat chromosomes 6 and Y are of primary importance for specific aspects of ventilatory control.
- Consomic rat strains are effective for dissecting the genetic architecture of complex physiological traits like respiratory control.
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