Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges

J Invest Dermatol. 2008 Jan;128(1):79-86. doi: 10.1038/sj.jid.5701011. Epub 2007 Aug 2.


Atopic dermatitis (AD) is a chronic dermatosis bearing clinical, histological, and immunologic similarities to chronic allergic contact dermatitis (ACD). AD shows a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels, a permeability barrier abnormality, and Staphylococcus aureus colonization. Repeated hapten challenges reportedly produce a Th2-like hypersensitivity reaction (Th2-like HR). Here, 9-10 challenges with oxazolone (Ox) to hairless mice also produced a chronic Th2-like HR. Permeability barrier function and expression of differentiation proteins, filaggrin, loricrin, and involucrin, became abnormal. CRTH-positive Th2-dominant inflammatory infiltrate, with increased IL-4 expression, and a large increase in serum IgE levels were observed. The barrier abnormality was associated with decreased stratum corneum (SC) ceramide content and impaired lamellar body secretion, resulting in abnormal lamellar membranes, as in human AD. Furthermore, as in human AD, epidermal serine protease activity in SC increased and expression of two lamellar body-derived antimicrobial peptides, CRAMP and mBD3, declined after Ox challenges, paralleling the decrease of their human homologues in AD. Thus, multiple Ox challenges to normal murine skin produce a chronic Th2-like HR, with multiple features of human AD. Because of its reproducibility, predictability, and low cost, this model could prove useful for evaluating both pathogenic mechanisms and potential therapies for AD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / analysis
  • Cathelicidins
  • Ceramides / analysis
  • DNA-Binding Proteins / analysis
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / metabolism
  • Disease Models, Animal
  • Female
  • Filaggrin Proteins
  • Haptens / administration & dosage*
  • Haptens / immunology
  • Immunity, Innate / drug effects
  • Immunoglobulin E / blood
  • Lipids / analysis
  • Mice
  • Mice, Hairless
  • Oxazolone / administration & dosage*
  • Oxazolone / immunology
  • Permeability
  • Serine Endopeptidases / metabolism
  • Th2 Cells / immunology
  • Transcription Factors / analysis


  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Ceramides
  • DNA-Binding Proteins
  • FLG protein, human
  • Filaggrin Proteins
  • Haptens
  • Lipids
  • Mbd3 protein, mouse
  • Transcription Factors
  • Oxazolone
  • Immunoglobulin E
  • Serine Endopeptidases