APStracts 8:0009A, 2001.

Variation in acute hypoxic ventilatory response is linked to mouse chromosome 9. Tankersley, Clarke G. Department of Environmental Health Sciences, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205

APStracts 8:0009A, 2001.

Genetic determinants confer variation among inbred mouse strains with respect to the magnitude and pattern of breathing during acute hypoxic challenge. Specifically, inheritance patterns derived from C3H/HeJ (C3) and C57BL/6J (B6) parental strains suggest that differences in hypoxic ventilatory response (HVR) are controlled by as few as two genes. The present study demonstrates that at least one genetic determinant is located on mouse chromosome 9. This genotype-phenotype association was established by phenotyping 52 B6C3F2 (F2) offspring for HVR characteristics. A genome-wide screen was performed using microsatellite DNA markers (n = 176) polymorphic between C3 and B6 mice. By computing log-likelihood values (LOD scores), linkage analysis compared marker genotypes with minute ventilation (Ťveť), tidal volume (Vt), and mean inspiratory flow (Vt/Ti, where Ti is inspiratory time) during acute hypoxic challenge (inspired O2 fraction = 0.10, inspired CO2 fraction = 0.03 in N2). A putative quantitative trait locus (QTL) positioned in the vicinity of D9Mit207 was significantly associated with hypoxic Ťveť (LOD = 4.5), Vt (LOD = 4.0), and Vt/Ti (LOD = 5.1). For each of the three HVR characteristics, the putative QTL explained more than 30% of the phenotypic variation among F2 offspring. In conclusion, this genetic model of differential HVR characteristics demonstrates that a locus ~33 centimorgans from the centromere on mouse chromosome 9 confers a substantial proportion of the variance in Ťveť, Vt, and Vt/Ti during acute hypoxic challenge.

Received 9 June 2000; accepted in final form 27 October 2000
APS Manuscript Number A978-0.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 January 2001