title: Gene expression analysis of atopic dermatitis-like skin lesions induced in NC/Nga mice by mite antigen stimulation under specific pathogen-free conditions.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a chronic relapsing inflammation characterized by pruritic and eczematous skin lesions usually observed in patients with a familial history of atopic diseases, but its exact etiology is unclear. An animal model is indispensable for the analysis of the pathogenesis and the development of new drugs to treat this disease. Here, we compare changes in gene expression profiles in the AD-like skin lesions of NC/Nga or BALB/c mice stimulated intradermally by mite antigen under specific pathogen-free (SPF) conditions.
  
  
  METHODS
  Mite Extract-Dp was injected intradermally into the right and left pinnae and into the skin of the back of NC/Nga or BALB/c mice in 2 places once per 3 days, and the clinical symptoms and the ear thickness were measured. On day 14 or day 28 after starting mite extract injection, we collected plasma and pinnae from NC/Nga or BALB/c mice. The amount of total immunoglobulin E (IgE) in plasma was assayed. We analyzed mRNA transcripts in pinnae using real-time quantitative PCR for the murine counterparts of several known allergy-related genes. Moreover, genome-wide gene expression in pinnae from NC/Nga mice was analyzed using high-density oligonucleotide arrays (GeneChip, Affymetrix).
  
  
  RESULTS
  From 2 weeks after stimulation, marked skin inflammation was induced in the pinnae of NC/Nga but not BALB/c mice. However, IgE levels in sera rose equally in both strains. Quantitative PCR analysis and comprehensive GeneChip analysis of the AD-like pinna skin lesions revealed that their development was accompanied by changes in expression of more than 1,000 genes. These included cytokines, cytokine receptors, proteases, and adhesion molecules. Furthermore, genes thus far not reported in association with AD were also affected.
  
  
  CONCLUSIONS
  From these results, the NC/Nga mouse model using mite sensitization under SPF conditions could be useful for elucidating the mechanisms of AD pathogenesis and developing more effective therapy for AD.
authors.affiliation: Genox Research, Inc., Tsukuba-shi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Heishi
authors.forename: Yukiho
authors.initials: Y
authors.lastname: Imai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Katayama
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hashida
authors.forename: Mikito
authors.initials: M
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Shinagawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004423:Ear / Q000473:pathology; D004487:Edema / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008925:Mites / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; C451163:Dermatophagoides pteronyssinus antigen p 2; D020382:Interleukin-18; D007073:Immunoglobulin E; D012313:RNA