A Mouse Model of Celiac Disease

Valérie Abadie, Chaitan Khosla, Bana Jabri

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The design and use of mouse models that reproduce key features of human diseases are critical to advance our understanding of the pathogenesis of autoimmune diseases and to test new therapeutic strategies. Celiac disease is a unique organ-specific autoimmune-like disorder occurring in genetically susceptible individuals carrying HLA-DQ2 or HLA-DQ8 molecules who consume gluten. The key histological characteristic of the disease in humans is the destruction of the lining of the small intestine, a feature that has been difficult to reproduce in immunocompetent animal models. This unit describes the DQ8-Dd-villin-IL-15 transgenic mouse model of CeD, which was engineered based on the knowledge acquired from studying CeD patients’ intestinal samples, and which represents the first animal model that develops villous atrophy in an HLA- and gluten-dependent manner without administration of any adjuvant. We provide detailed protocols for inducing and monitoring intestinal tissue damage, evaluating the cytotoxic properties of intraepithelial lymphocytes that mediate enterocyte lysis, and assessing the activation of the enzyme transglutaminase 2, which contributes to the generation of highly immunogenic gluten peptides. Detailed protocols to prepare pepsin-trypsin digested gliadin (PT-gliadin) or chymotrypsin-digested gliadin (CT-gliadin), which allow antibody detection against native or deamidated gluten peptides, are also provided in this unit.

Original languageEnglish
Article numbere515
JournalCurrent Protocols
Volume2
Issue number8
DOIs
StatePublished - Aug 2022
Externally publishedYes

Keywords

  • celiac disease
  • intraepithelial lymphocytes
  • mouse model
  • transglutaminase 2
  • villous atrophy

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