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J Appl Physiol 92: 1277-1284, 2002. First published November 16, 2001; doi:10.1152/japplphysiol.00609.2001
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Vol. 92, Issue 3, 1277-1284, March 2002

Differential CO2-induced c-fos gene expression in the nucleus tractus solitarii of inbred mouse strains

Clarke G. Tankersley1, Musa A. Haxhiu3, and Estelle B. Gauda2

1 Department of Environmental Health Sciences, Bloomberg School of Public Health, and 2 Department of Pediatrics, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205; and 3 Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, District of Columbia 20059

Genetic determinants confer variation between inbred mouse strains with respect to the magnitude and pattern of ventilation during hypercapnic challenge. Specifically, inheritance patterns derived from low-responsive C3H/HeJ (C3) and high-responsive C57BL/6J (B6) mouse strains suggest that differential hypercapnic ventilatory sensitivity (HCVS) is controlled by two independent genes. The present study also tests whether differential neuronal activity in respiratory control regions of the brain is positively associated with strain variation in HCVS. With the use of whole body plethysmography, ventilation was assessed in C3 and B6 strains at baseline and during 30 min of hypercapnia (inspired CO2 fraction = 0.15, inspired O2 fraction = 0.21 in N2). Subsequently, in situ hybridization histochemistry was performed to determine changes in c-fos gene expression in the commissural subnucleus of the nucleus tractus solitarius (NTS). During hypercapnia, breathing frequency and tidal volume were significantly (P < 0.01) different between strains: C3 mice showed a slow, deep-breathing pattern relative to a rapid, shallow phenotype of B6 mice. CO2-induced increase in c-fos gene expression was significantly (P < 0.01) greater in NTS regions of B6 compared with C3 mice. In this genetic model of differential HCVS, the results suggest that a genomic basis for varied hypercapnic chemoreception or transduction confers greater afferent neuronal activity in the caudal NTS for high-responsive B6 mice compared with low-responsive C3 mice.

C3H/HeJ; C57BL/6J; hypoventilation; hypercapnic ventilation; control of breathing


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