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J Appl Physiol (May 10, 2007). doi:10.1152/japplphysiol.01253.2006
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Submitted on November 6, 2006
Accepted on May 8, 2007

Methacholine Responsiveness in Mice from 2 to 8 weeks of age

Elizabeth M Bozanich1, Tibor Janosi2, Rachel A Collins1, Cindy Thamrin3, Debra Jane Turner1, Zoltan Hantos2, and Peter D. Sly1*

1 Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Perth, Western Australia, Australia
2 Department of Medical Informatics and Engineering, University of Szeged, H-6720 Szeged, Hungar, Hungary
3 Perth, Western Australia, Australia; Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Perth, Western Australia, Australia

* To whom correspondence should be addressed. E-mail: peters{at}ichr.uwa.edu.au.

Many chronic human lung diseases have their origin in early childhood yet most murine models used to study them utilize adult mice. An important component of the asthma phenotype is exaggerated airway responses, frequently modelled by methacholine (MCh) challenge. The present study was undertaken to characterize MCh responses in mice from 2 to 8 weeks of age measuring absolute lung volume and volume-corrected respiratory mechanics as outcome variables. Female BALB/c mice aged 2, 3, 4, 6 & 8 weeks were studied during cumulative intravenous MCh challenge. Following each MCh dose absolute lung volume was measured plethysmographically at functional residual volume (FRC) and during a slow inflation to 20 hPa transrespiratory pressure. Respiratory system impedance (Zrs) was measured continuously during the inflation manoeuvre and partitioned into airway and constant phase parenchymal components by model fitting. Volume-corrected (specific) estimates of respiratory mechanics were calculated. Intravenous MCh challenge induced a predominantly airway response with no evidence of airway closure in any age group. No changes in FRC were seen in mice of any age during the MCh challenge. The specific airway resistance MCh dose response curves did not show significant differences between the age groups. The results from the present study do not show systematic differences in MCh responsiveness in mice from 2 to 8 weeks of age.




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