title: Lung disease in the cystic fibrosis mouse exposed to bacterial pathogens.
abstract: Lung disease is the major cause of death in cystic fibrosis (CF), but there is no evidence for overt lung involvement at birth. We show here that the same is true for the gene targeted cftrm1HGU mutant mouse. Furthermore, this CF mouse model demonstrates an impaired capacity to clear Staphylococcus aureus and Burkholderia (Pseudomonas) cepacia, two opportunistic lung pathogens closely associated with lung disease in CF subjects. The cftrm1HGU homozygotes display mucus retention and frank lung disease in response to repeated microbial exposure. Thus, lung disease in the cftrm1HGU mouse develops in response to bacterial infection, establishing a model to dissect the pathogenesis of CF pulmonary disease and providing a clinically relevant end point to assess the efficacy of pharmacologic or genetic interventions.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Davidson
authors.forename: J R
authors.initials: JR
authors.lastname: Dorin
authors.forename: G
authors.initials: G
authors.lastname: McLachlan
authors.forename: V
authors.initials: V
authors.lastname: Ranaldi
authors.forename: D
authors.initials: D
authors.lastname: Lamb
authors.forename: C
authors.initials: C
authors.lastname: Doherty
authors.forename: J
authors.initials: J
authors.lastname: Govan
authors.forename: D J
authors.initials: DJ
authors.lastname: Porteous
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000209:etiology* / Q000473:pathology; D016956:Burkholderia cepacia; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D006720:Homozygote; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009894:Opportunistic Infections / Q000209:etiology* / Q000473:pathology; D011552:Pseudomonas Infections / Q000209:etiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000209:etiology / Q000473:pathology