Genetic determinants on rat chromosome 6 modulate variation in the hypercapnic ventilatory response using consomic strains.
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 CO(2) 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% CO(2) 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.
Dwinell
M R
MR
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. mrdwinel@mcw.edu
Forster
H V
HV
Petersen
J
J
Rider
A
A
Kunert
M P
MP
Cowley
A W
AW
Jacob
H J
HJ
D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers / Q000235:genetics / Q000502:physiology*; D014644:Genetic Variation / Q000235:genetics / Q000502:physiology; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006935:Hypercapnia / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D012123:Pulmonary Ventilation / Q000235:genetics* / Q000502:physiology; D013045:Species Specificity
D005819:Genetic Markers