title: Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load.
abstract: OBJECTIVE
  To establish the role of defects in murine Cftr in the susceptibility to Staphylococcus aureus lung disease using mouse models of cystic fibrosis (CF), congenic or inbred strains.
  
  
  METHODS
  We describe the histopathological analyses of CF mice repeatedly exposed by aerosolisation to a CF isolate of S. aureus, using residual function Cftr mice and compound heterozygotes generated by intercrossing these with Cftr 'null' mice, all congenic on the C57Bl6/N background.
  
  
  RESULTS
  We demonstrate that mice congenic on the C57Bl/6 background develop significantly more severe lung pathology than non-CF littermates in response to repeated exposure to the most frequent early CF lung pathogen S. aureus. Furthermore, reducing the level of Cftr by half in compound heterozygote mice does not impact upon disease severity, even in response to an increased bacterial dose.
  
  
  CONCLUSIONS
  These results are consistent with an airway clearance defect, or abnormal inflammatory response secondary to Cftr mutation. These studies confirm the primary role for Cftr mutation in the development of this lung phenotype. In addition, these results demonstrate that a further 50% decrease in residual wild-type Cftr mRNA levels in this model does not impact the severity of the histopathological response to S. aureus, suggesting a critical threshold level for functional CFTR.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.forename: Sheila
authors.initials: S
authors.lastname: Webb
authors.forename: Peter
authors.initials: P
authors.lastname: Teague
authors.forename: John R W
authors.initials: JR
authors.lastname: Govan
authors.forename: Julia R
authors.initials: JR
authors.lastname: Dorin
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D008168:Lung / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D018345:Mice, Knockout; D009154:Mutation; D013203:Staphylococcal Infections / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator