title: Acute intratracheal Pseudomonas aeruginosa infection in cystic fibrosis mice is age-independent.
abstract: BACKGROUND
  Since the discovery of the human CFTR gene in 1989 various mouse models for cystic fibrosis (CF) have been generated and used as a very suitable and popular tool to approach research on this life-threatening disease. Age related changes regarding the course of disease and susceptibility towards pulmonary infections have been discussed in numerous studies.
  
  
  METHODS
  Here, we investigated CftrTgH(neoim)Hgu and Cftrtm1Unc-Tg(FABPCFTR)1Jaw/J CF mice and their non-CF littermates during an acute lung infection with Pseudomonas aeruginosa for age dependent effects of their lung function and immune response.Mice younger than three or older than six months were intratracheally infected with P. aeruginosa TBCF10839. The infection was monitored by lung function of the animals using non-invasive head-out spirometry and the time course of physiological parameters over 192 hours. Quantitative bacteriology and lung histopathology of a subgroup of animals were used as endpoint parameters.
  
  
  RESULTS
  Age-dependent changes in lung function and characteristic features for CF like a shallower, faster breathing pattern were observed in both CF mouse models in uninfected state. In contrast infected CF mice did not significantly differ from their non-CF littermates in susceptibility and severity of lung infection in both mouse models and age groups. The transgenic Cftrtm1Unc-Tg(FABPCFTR)1Jaw/J and their non-CF littermates showed a milder course of infection than the CftrTgH(neoim)Hgu CF and their congenic C57Bl/6J non-CF mice suggesting that the genetic background was more important for outcome than Cftr dysfunction.
  
  
  CONCLUSIONS
  Previous investigations of the same mouse lines have shown a higher airway susceptibility of older CF mice to intranasally applied P. aeruginosa. The different outcome of intranasal and intratracheal instillation of bacteria implies that infected CF epithelium is impaired during the initial colonization of upper airways, but not in the subsequent response of host defense.
authors: Clinical Research Group, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany. munder.antje@mh-hannover.de
authors: Antje
authors: A
authors: Munder
authors: Florian
authors: F
authors: Wölbeling
authors: Tanja
authors: T
authors: Kerber-Momot
authors: Dirk
authors: D
authors: Wedekind
authors: Ulrich
authors: U
authors: Baumann
authors: Erich
authors: E
authors: Gulbins
authors: Burkhard
authors: B
authors: Tümmler
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D003550:Cystic Fibrosis / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012129:Respiratory Function Tests; D014136:Tracheitis / Q000276:immunology* / Q000382:microbiology
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator