title: Cornulin, a marker of late epidermal differentiation, is down-regulated in eczema.
abstract: BACKGROUND
  Eczema is a common chronic inflammatory skin disorder which shows strong genetic predisposition. To identify new potential molecular determinants of the disease pathogenesis, we performed a gene expression study in an eczema mouse model. This analysis identified a marked down regulation of the cornulin gene (CRNN), a member of the epidermal differentiation complex, in the eczema-like skin. We then investigated CRNN as an eczema candidate gene and studied its polymorphism and the expression in the skin of eczema patients.
  
  
  METHODS
  An eczema-like phenotype was induced in mice by allergen (Der p2) patching. Gene expression analysis was performed with the subtractive suppression hybridization method and validated by real time PCR and the transmission disequilibrium test was used to test for genetic associations in 406 multiplex eczema families.
  
  
  RESULTS
  Der p 2 patched mice developed a localized eczema and a Th 2 skewed systemic response. Real time PCR analysis confirmed a down regulation of CRNN mRNA in eczema-like skin in the mouse model and in human eczema. The CRNN polymorphism rs941934 was significantly associated with atopic eczema in the genetic analysis (P = 0.006), though only as part of an extended haplotype including a known associated variant (2282del4) in the filaggrin gene.
  
  
  CONCLUSIONS
  CRNN mRNA expression is decreased in eczematous skin. Further studies are needed to verify whether the associated cornulin polymorphism contribute to the genetic susceptibility in eczema.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Liedén
authors.forename: E
authors.initials: E
authors.lastname: Ekelund
authors.forename: I-C
authors.initials: IC
authors.lastname: Kuo
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: C-H
authors.initials: CH
authors.lastname: Huang
authors.forename: L
authors.initials: L
authors.lastname: Mallbris
authors.forename: S P
authors.initials: SP
authors.lastname: Lee
authors.forename: L K
authors.initials: LK
authors.lastname: Seng
authors.forename: G Y
authors.initials: GY
authors.lastname: Chin
authors.forename: C-F
authors.initials: CF
authors.lastname: Wahlgren
authors.forename: C N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: B
authors.initials: B
authors.lastname: Björkstén
authors.forename: M
authors.initials: M
authors.lastname: Ståhle
authors.forename: M
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: M
authors.initials: M
authors.lastname: Nordensköld
authors.forename: M
authors.initials: M
authors.lastname: Bradley
authors.forename: K Y
authors.initials: KY
authors.lastname: Chua
authors.forename: M
authors.initials: M
authors.lastname: D'Amato
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics*; D004817:Epidermis / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D000091344:Filaggrin Proteins; D015870:Gene Expression; D005786:Gene Expression Regulation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000175:diagnosis / Q000235:genetics / Q000276:immunology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C418764:CRNN protein, human; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D005819:Genetic Markers; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D007073:Immunoglobulin E