Genetic control of susceptibility to ozone-induced changes in mouse tracheal electrophysiology.
Genetic factors influence the responses of humans and rodents to ozone (O3) inhalation. We previously demonstrated differential O3-induced decreases of tracheal potential (VT) in C57BL/6J (B6) and C3H/HeJ (C3) strain mice. To characterize the genetic basis of this strain-specific response, we measured VT in progeny of B6 and C3 strain mice and in six additional inbred strains of mice 6 h after O3 exposures (2 ppm x 3 h). First filial generation (F1) mice and second generation backcrosses with the resistant parent were uniformly resistant. The distribution of VT in second generation backcrosses with the susceptible parent resembled that of a population composed of resistant and susceptible mice in a 1:1 ratio. These data suggested simple autosomal recessive inheritance of susceptibility. However, overlapping distributions prevented statistical confirmation of that hypothesis. Strain screening revealed a susceptible phenotype in 129/J, A/J, B6, C3HeB/FeJ, and SJL/J and a resistant phenotype in AKR/J, C3, and CBA/J inbred mouse strains. Because this pattern of susceptibility to changes in VT differs from that of susceptibility to lung inflammation, the genetic factors that determine these two responses to acute O3 are not identical.
Takahashi
M
M
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Kleeberger
S R
SR
Croxton
T L
TL
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D004594:Electrophysiology; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000166:cytology; D010126:Ozone / Q000494:pharmacology*; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D010126:Ozone