Cornulin, a marker of late epidermal differentiation, is down-regulated in eczema

A. Liedén, E. Ekelund, I. C. Kuo, I. Kockum, C. H. Huang, L. Mallbris, S. P. Lee, L. K. Seng, G. Y. Chin, C. F. Wahlgren, C. N.A. Palmer, B. Björkstén, M. Ståhle, M. Nordensköld, M. Bradley, K. Y. Chua, M. D'Amato

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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.

Original languageEnglish
Pages (from-to)304-311
Number of pages8
JournalAllergy
Volume64
Issue number2
DOIs
Publication statusPublished - 1 Feb 2009
Externally publishedYes

Keywords

  • Animal models
  • Apoptosis
  • Atopic dermatitis
  • Epithelium
  • Genetics

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