title: Nasal abnormalities in cystic fibrosis mice independent of infection and inflammation.
abstract: It is not known whether the progressive airway changes in cystic fibrosis (CF) are all secondary to infection and inflammation. The CF mouse nose shares electrophysiologic and cellular properties with human CF airway epithelium. In the present work, we tested the hypothesis that structural abnormalities in the nasal mucosa of CF mice develop independent of infection and inflammation. We performed nasal lavage and subsequent serial coronal section through the nasal tissue of adult CF (mutations Cftr(TgHm1G551D) and Cftr(tm1Unc)-TgN((FABPCFTR))) and wild-type mice raised under normal housing conditions. Nasal tissue was also obtained from Day 17 embryos and newborn pups. Detailed histologic examination of the respiratory and olfactory epithelium within the nasal cavity was performed. Bacterial culture, cell count, and macrophage inflammatory protein-2 (MIP-2) concentration were assessed in nasal lavage fluid. Significantly thickened respiratory epithelium and increased mucous cell density was found in adult CF mice of both mutations compared with wild-type animals. In contrast, the olfactory epithelium was thinner, with a decreased cell density. Areas of lymphoid aggregates were found in CF mice but not in non-CF mice. There were no differences in bacterial growth, cell count, or MIP-2 concentrations. No genotype differences were observed in the embryonic or newborn periods. There are significant histologic changes in the nasal mucosa of adult CF mice, not associated with increased lumenal inflammation or bacterial content, and which are not present perinatally. These may be novel therapeutic targets.
authors.affiliation: Department of Gene Therapy, Emmanuel Kaye Building, 1b Manresa Road, London SW3 6LR, UK.
authors.forename: Tom N
authors.initials: TN
authors.lastname: Hilliard
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Ray
authors.initials: R
authors.lastname: Farley
authors.forename: Sara
authors.initials: S
authors.lastname: Escudero-Garcia
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Wainwright
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jeffery
authors.forename: Uta
authors.initials: U
authors.lastname: Griesenbach
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
authors.forename: Eric W F W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004195:Disease Models, Animal; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007239:Infections / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009666:Nose / Q000002:abnormalities* / Q000473:pathology*; D009831:Olfactory Mucosa / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D020545:Respiratory Mucosa / Q000473:pathology
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator