Faculty Collaboration Database

Do genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to regulation of breathing? Respir Physiol Neurobiol 2003 May 30;135(2-3):247-61

Date

06/18/2003

Pubmed ID

12809624

DOI

10.1016/s1569-9048(03)00042-9

Scopus ID

2-s2.0-0038384573 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

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.

Author List

Forster HV, Dwinell MR, Hodges MR, Brozoski D, Hogan GE

Authors

Melinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Hubert V. Forster PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Body Temperature
Chromosomes
Exercise
Female
Heart Rate
Homozygote
Humans
Hypercapnia
Hypoxia
Male
Phenotype
Pulmonary Ventilation
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Respiration
Sex Characteristics
Species Specificity
Tidal Volume
Time Factors