Establishment and Evaluation of a BALB/c Mouse Model of Celiac Disease Caused by Dietary Gluten

Objective: A mouse model of celiac disease induced by gluten was established and its feasibility was evaluated by testing diagnostic indicators of celiac disease. Methods: Female BALB/c mice aged 6-8 weeks fed a gluten-free diet for more than three generations were randomly divided into two groups, control and celiac disease (CeD). On the first day of the experiment, the mice in the CeD group were fed a gluten-containing diet (2.5 g/kg) instead of the gluten-free diet for 30 days while those in the control group were still fed the gluten-free diet. In the first three weeks, each mouse in the CeD group was intraperitoneally injected with 0.2 mL of 0.01 mol/L phosphate buffered saline containing 150 μg of gliadin twice a week. In the fourth week, the rear footpad of each mouse in this group was injected twice with 50 μg of gliadin emulsified in 50 μL of Freund's complete adjuvant (on the first and fourth days respectively). Fluorescein isothiocyanate-labeled dextran levels were used to indicate intestinal permeability in mice; real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of tight junction proteins (ZO-1, ZO-2 and claudin-1), inflammatory cytokines (interleukin(IL)-15, IFN-γ and IL-4) and immune cell marker genes (CD4, CD19 and CD138) in the duodenum; and the enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of total transglutaminase (tTG) and zonulin in duodenal tissue. Results: The intestinal barrier of the mice in the CeD group was damaged, the length of small intestinal villi was significantly decreased, the mRNA expression of the gene encoding transglutaminase 2 (TG2) was significantly increased(P < 0.05), and the relative expression levels of genes encoding cytokines and immune cell markers associated with celiac disease were notably increased compared with the control group. Conclusion: The animal model can effectively mimic the key clinical features of celiac disease as evidenced by intestinal pathology, intestinal barrier, and immune response. It may be used in future research to develop potential therapeutics for celiac disease. © 2022, China Food Publishing Company. All right reserved.