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 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.
Bonora
Monique
M
Laboratoire Physiologie Respiratoire, Faculté de Médecine Saint-Antoine, 70512 Paris, France. bonora@st-antoine.inserm.fr
Bernaudin
Jean-Francois
JF
Guernier
Claude
C
Brahimi-Horn
Marie Christiane
MC
D000818:Animals; D001835:Body Weight; D002245:Carbon Dioxide / Q000378:metabolism; D003243:Consciousness; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006935:Hypercapnia; D000860:Hypoxia; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR / Q000235:genetics*; D018345:Mice, Knockout; D012119:Respiration; D015656:Respiratory Mechanics; D012137:Respiratory System / Q000254:growth & development; D013990:Tidal Volume; D013997:Time Factors
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002245:Carbon Dioxide