Do genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to regulation of breathing?
As part of a large scale, high through-put physiologic genomics study, we sought to determine whether genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to phenotypic differences in the control of breathing between two inbred rat strains (SS/Mcw and BN/Mcw). Through a chromosomal substitution breeding strategy, we created 5 consomic rat strains (SS.BN9, SS.BN13, SS.BN16, SS.BN18, and SS.BN20), which were BN/Mcw homozygous at only one chromosome and SS/Mcw homozygous at all other chromosomes. Standard plethsmography was used to assess eupneic breathing and ventilatory responses to CO(2) (FI(CO(2))=0.07) and hypoxia (FI(CO(2))=0.12), and Pa(CO(2)) during treadmill exercises provided the index of the exercise hyperpnea. There were no robust differences in eupneic breathing between any strains. The ventilatory response to CO(2) was 150% greater (P<0.001) in the SS/Mcw rats than in the BN/Mcw rats and all consomic strains had the SS/Mcw phenotype. Hyperventilation during hypoxia did not differ between the parental and the consomic strains, but ventilation during hypoxia was greater (P<0.001) in the SS/Mcw than in the BN/Mcw, and the SS.BN9, and SS.BN18 appeared to acquire this BN/Mcw phenotype. The hyperventilation during treadmill walking was greater (P<0.006) in the BN/Mcw and the SS.BN18 rats than in the SS/Mcw rats. Finally, the duration of the apnea following an augmented breath (post sigh apnea, PSA) was greater (P<0.001) in the BN/Mcw and the SS.BN9 rats than all other strains. We conclude that the robust difference between the parental strains in ventilatory CO(2) sensitivity is not due to genotypic differences on the 5 chromosomes studied to date, but genotypic differences on chromosomes 9 and 18 contribute to differences in ventilatory responses to hypoxia, exercise, and/or to the differences in the PSA.
Forster
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Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, and Zablocki VA Medical Center, Milwaukee, WI 53226, USA. bforster@mcw.edu
Dwinell
M R
MR
Hodges
M R
MR
Brozoski
D
D
Hogan
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GE
D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D002875:Chromosomes / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D005260:Female; D006339:Heart Rate; D006720:Homozygote; D006801:Humans; D006935:Hypercapnia / Q000235:genetics / Q000503:physiopathology; D000860:Hypoxia / Q000235:genetics / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D012123:Pulmonary Ventilation; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012119:Respiration / Q000235:genetics*; D012727:Sex Characteristics; D013045:Species Specificity; D013990:Tidal Volume; D013997:Time Factors