title: Functional characterization of a porcine emphysema model.
abstract: BACKGROUND
  Lung emphysema is a central feature of chronic obstructive pulmonary disease (COPD), a frequent human disease worldwide. Cigarette smoking is the major cause of COPD, but genetic predisposition seems to be an important factor. Mutations in surfactant protein genes have been linked to COPD phenotypes in humans. Also, the catalytic activities of metalloproteinases (MMPs) are central in the pathogenesis of emphysema/COPD. Especially MMP9, but also MMP2, MMP7, and MMP12 seem to be involved in human emphysema. MMP12-/- mice are protected from smoke-induced emphysema. ITGB6-/- mice spontaneously develop age-related lung emphysema due to lack of ITGB6-TGF-β1 regulation of the MMP12 expression.
  
  
  METHODS
  A mutated pig phenotype characterized by age-related lung emphysema and resembling the ITGB6-/- mouse has been described previously. To investigate the emphysema pathogenesis in this pig model, we examined the expression of MMP2, MMP7, MMP9, MMP12, and TGF-β1 by quantitative PCR (qPCR). In addition, immunohistochemical stainings of the lungs with SP-B, SP-C, MMP9, and MMP12 antibodies were performed. The haematologic/immunologic status of the pigs also was studied.
  
  
  RESULTS
  The qPCR study showed no difference between pigs with and without emphysema, and no systemic differences were indicated by the haematologic and immunologic studies. However, the immunohistochemical stainings showed an increased expression of MMP9 and MMP12 in older, mutated pigs (with emphysema) compared with normal and young mutated pigs (without emphysema).
  
  
  CONCLUSIONS
  The pig model is comparable to human emphysema patients and the ITGB6-/- mouse model with respect to both morphology and functionality.
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark, cvb@sund.ku.dk.
authors.forename: Camilla Sichlau
authors.initials: CS
authors.lastname: Bruun
authors.forename: Louise Kruse
authors.initials: LK
authors.lastname: Jensen
authors.forename: Páll Skuli
authors.initials: PS
authors.lastname: Leifsson
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.forename: Susanna
authors.initials: S
authors.lastname: Cirera
authors.forename: Claus Bøttcher
authors.initials: CB
authors.lastname: Jørgensen
authors.forename: Henrik Elvang
authors.initials: HE
authors.lastname: Jensen
authors.forename: Merete
authors.initials: M
authors.lastname: Fredholm
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053508:Matrix Metalloproteinase 12 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D039641:Integrin beta Chains; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C072170:integrin beta6; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12
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