Ventilatory responses to hypercapnia and hypoxia in conscious cystic fibrosis knockout mice Cftr-/-

This study was designed to examine the ventilatory performance and the lung histopathology of cystic fibrosis knockout mice (Cftr(-/-)) compared with heterozygous (Cftr(+/-)) or wildtype (Cftr(+/+)) littermates. Ventilation was recorded in conscious animals using whole-body plethysmography. Tidal Volume (V-T), respiratory frequency (f), and minute ventilation (V-E) 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% O-2). The results for Cftr(+/-) and Cftr(+/+) were pooled into one control group because they did not differ. In air and in response to hypercapnia, V-E, V-T, and f were similar in Cftr(-/-) mice and in controls. During graded hypoxia, V, was decreased in Cftr(-/-) mice at 10 and 8% 0, 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.