Abstract
This study was designed to examine the ventilatory performance and the lung histopathology of cystic fibrosis knockout mice (Cftr−/−) compared with heterozygous (Cftr+/−) or wild-type (Cftr+/+) littermates. Ventilation was recorded in conscious animals using whole-body plethysmography. Tidal volume (VT), respiratory frequency (f), and minute ventilation (VE) were measured during air breathing and in response to various levels of hypercapnia (2, 4, 6, or 8% CO2) or hypoxia (14, 12, 10, or 8% O2). The results for Cftr+/− and Cftr+/+ were pooled into one control group because they did not differ. In air and in response to hypercapnia, VE, VT, and f were similar in Cftr+/+ in controls. During graded hypoxia, VE was decreased in Cftr−/− mice and mice at 10 and 8% O2 because of a lower f. Histology showed neither inflammation nor obstruction of airways in Cftr−/− mice. Morphometric analysis showed alveolar dilation as a result of either distension or impaired development. In conclusion, cystic fibrosis knockout mice have normal baseline breathing and ventilatory response to hypercapnia but a decreased ventilatory response to severe hypoxia. This latter result associated with the morphometric analysis suggests that Cftr−/− mice may exhibit immaturity of the respiratory system.
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Abbreviations
- Cftr:
-
cystic fibrosis transmembrane conductance regulator
- CF:
-
cystic fibrosis
- VE:
-
minute ventilation
- VT:
-
tidal volume
- f:
-
respiratory frequency
- BW:
-
body weight
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Acknowledgements
We thank members of the CNRS Center de Développement des Techniques Avancées pour l'Experimentation Animale (Orléans, France), in particular M.-F. Bertrand, for providing the mice, J. Chandellier for preparing the illustrations, and Lydie Germain and Nicole Maurin for help in morphometric analysis. We are also grateful to Prof. H. Gautier for advice and useful suggestions.
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This work was supported by grants from the Association “Vaincre la Mucoviscidose” (Grant SI A 98001) and UPRES (EA 2397 and EA 34997).
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Bonora, M., Bernaudin, JF., Guernier, C. et al. Ventilatory Responses to Hypercapnia and Hypoxia in Conscious Cystic Fibrosis Knockout Mice Cftr−/−. Pediatr Res 55, 738–746 (2004). https://doi.org/10.1203/01.PDR.0000117841.81730.2B
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DOI: https://doi.org/10.1203/01.PDR.0000117841.81730.2B
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