title: Early pulmonary disease manifestations in cystic fibrosis mice.
abstract: Altered pulmonary function is present early in the course of cystic fibrosis (CF), independent of documented infections or onset of pulmonary symptoms. New initiatives in clinical care are focusing on detection and characterization of preclinical disease. Thus, animal models are needed which recapitulate the pulmonary phenotype characteristic of early stage CF.
  
  
  
  We investigated young CF mice to determine if they exhibit pulmonary pathophysiology consistent with the early CF lung phenotype. Lung histology and pulmonary mechanics were examined in 12- to 16-week-old congenic C57bl/6 F508del and R117H CF mice using a forced oscillation technique (flexiVent).
  
  
  
  There were no significant differences in the resistance of the large airways. However, in both CF mouse models, prominent differences in the mechanical properties of the peripheral lung compartment were identified including decreased static lung compliance, increased elastance and increased tissue damping. CF mice also had distal airspace enlargement with significantly increased mean linear intercept distances.
  
  
  
  An impaired ability to stretch and expand the peripheral lung compartment, as well as increased distances between gas exchange surfaces, were present in young CF mice carrying two independent Cftr mutations. This altered pulmonary histopathophysiology in the peripheral lung compartment, which develops in the absence of infection, is similar to the early lung phenotype of CF patients.
authors.affiliation: Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, United States. Electronic address: rjm11@case.edu.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Darrah
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Mitchell
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Cara K
authors.initials: CK
authors.lastname: Campanaro
authors.affiliation: Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Barbato
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Litman
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Abdus
authors.initials: A
authors.lastname: Sattar
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hodges
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Drumm
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Medicine, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, United States.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Jacono
mesh_terms: D000818:Animals; D058070:Asymptomatic Diseases; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004195:Disease Models, Animal; D008168:Lung / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012129:Respiratory Function Tests / Q000379:methods
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Cystic fibrosis; Lung mechanics; Mouse models