Autosomal recessive inheritance of airway hyperreactivity to 5-hydroxytryptamine.
We have previously reported that airway hyperresponsiveness to acetylcholine (ACh) is inherited as an autosomal recessive trait in A/J and C3H/HeJ mice and the progeny of crosses between them (FASEB J. 2: 2605-2608, 1988). In the present report, we have extended these studies by evaluating the biological variability in the airway response to 5-hydroxytryptamine (5-HT) and ACh among multiple genetically standardized inbred strains of mice. The pattern of airway responsiveness to ACh differed significantly from that of 5-HT in nine inbred strains of mice. A/J mice showed nonspecific airway hyperresponsiveness to both 5-HT and ACh. DBA/2J mice were hyperresponsive to 5-HT but not to ACh. An airway phenotype that resembled these inbred strains is termed HYPERREACTIVE. The C3H/HeJ and C57BL/6J inbred strains were minimally reactive to either ACh or 5-HT. Airway phenotypes that resembled these minimally reactive strains are termed HYPOREACTIVE. The frequency of HYPERRACTIVE and HYPOREACTIVE offspring from crosses between A/J and C3H/HeJ mice or DBA/2J and C57BL/6J mice is consistent with a single autosomal recessive gene, primarily determining airway hyperresponsiveness to 5-HT. We report linkage studies which suggest that these genes are not closely linked and that 5-HT and ACh airway hyperresponsiveness is inherited independently. The results of these studies suggest that murine nonspecific airway hyperresponsiveness is determined by multiple genes.
Levitt
R C
RC
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Mitzner
W
W
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D012119:Respiration / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D013045:Species Specificity
D012701:Serotonin; D000109:Acetylcholine