A Mouse Model of Celiac Disease

Area of Science:

• Immunology
• Gastroenterology
• Animal Models

Background:

• Celiac disease (CeD) is an autoimmune disorder triggered by gluten in genetically susceptible individuals.
• Reproducing key CeD features, like villous atrophy, in animal models has been challenging.
• Existing models often require adjuvants, limiting their relevance to human disease.

Purpose of the Study:

• To describe a novel transgenic mouse model (DQ8-D^d -villin-IL-15tg) that replicates key aspects of human celiac disease.
• To provide detailed protocols for inducing, monitoring, and analyzing CeD-like pathology in this model.
• To facilitate research into CeD pathogenesis and therapeutic strategies.

Main Methods:

• Engineering DQ8-D^d -villin-IL-15 transgenic mice based on human CeD patient data.
• Detailed protocols for inducing and monitoring intestinal tissue damage, including villous atrophy.
• Assessing cytotoxic intraepithelial lymphocytes and transglutaminase 2 activation.
• Methods for preparing specific gluten peptide digests (PT-gliadin, CT-gliadin) for antibody detection.

Main Results:

• The DQ8-D^d -villin-IL-15tg mouse model develops villous atrophy in a human leukocyte antigen (HLA)- and gluten-dependent manner.
• This model is the first to show gluten-induced villous atrophy without adjuvant administration.
• Protocols enable detailed analysis of disease mechanisms, including immune cell cytotoxicity and enzyme activation.

Conclusions:

• The DQ8-D^d -villin-IL-15tg mouse represents a significant advancement in modeling celiac disease.
• This model offers a valuable platform for studying CeD pathogenesis and evaluating novel therapeutic interventions.
• The provided protocols standardize research methods for celiac disease animal models.