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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-/- mice and in controls. During graded hypoxia, VE was decreased in Cftr-/- 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.

Ventilatory Responses to Hypercapnia and Hypoxia in Conscious Cystic Fibrosis Knockout Mice Cftr−/−