Genetic control of differential baseline breathing pattern

Tankersley, Clarke G., Robert S. Fitzgerald, Roy C. Levitt,Wayne A. Mitzner, Susan L. Ewart, and Steven R. Kleeberger. Genetic control of differential baseline breathing pattern. J. Appl. Physiol. 82(3): 874-881, 1997.The purpose of the present study was to determine the geneticcontrol of baseline breathing pattern by examining the mode ofinheritance between two inbred murine strains with differentialbreathing characteristics. Specifically, the rapid, shallow phenotypeof the C57BL/6J (B6) strain is consistently distinct from theslow, deep phenotype of the C3H/HeJ (C3) strain. The responsedistributions of segregant and nonsegregant progeny were compared withthe two progenitor strains to determine the mode of inheritance foreach ventilatory characteristic. The BXH recombinant inbred (RI)strains derived from the B6 and C3 progenitors were examined toestablish strain distribution patterns for each ventilatory trait. Toestablish the mode of inheritance, baseline breathing frequency (f),tidal volume, and inspiratory time(TI) were measured five timesin each of 178 mature male animals from the two progenitor strains andtheir progeny by using whole body plethysmography. With respect to fand TI, the two progenitor strains were consistently distinct, and segregation analyses of theinheritance pattern suggest that the most parsimonious genetic modelfor response distributions of f andTI is a two-loci model. Insimilar experiments conducted on 82 mature male animals from 12 BXH RIstrains, each parental phenotype was represented by one or more of theRI strains. Intermediate phenotypes emerged to confirm the likelihoodthat parental strain differences in f andTI were determined by more thanone locus. Taken together, these studies suggest that the phenotypicdifference in baseline respiratory timing between male B6 and C3 miceis best explained by a genetic model that considers at least two locias major determinants.