Inflammatory Diseases: IBD mouse model

Main characteristics

• Global IBD Score

  Throughout the study, mice are monitored daily or as needed to assess key clinical signs, including body weight loss, diarrhea, and rectal bleeding. These parameters are combined to calculate a comprehensive IBD clinical score, providing a consistent and quantitative measure of disease severity.

• Endoscopy

  Endoscopy offers valuable additional readouts in IBD studies by providing a detailed, real-time view of the colonic mucosa. It enables longitudinal monitoring of mucosal lesions, allowing for early and accurate detection of colitis, often before clinical scores reflect disease onset. Endoscopy also supports direct assessment of treatment efficacy over time and shows a strong correlation with histological findings, making it a powerful tool to complement clinical and tissue-based analyses.

• Histopathology

  as colon shortening is a hallmark of IBD-related inflammation. Tissues are then processed for histological analysis, typically using H&E staining, to assess and quantify key pathological features such as tissue damage, ulceration, and inflammatory cell infiltration. This provides a detailed and quantitative evaluation of disease severity at the tissue level.

• Human Immune Cell Infiltration

  The colon can also be analyzed to characterize and quantify human immune cell infiltration, either by flow cytometry following tissue dissociation or through immunohistochemistry (IHC). These complementary approaches provide detailed insights into immune cell composition, localization, and activation status within the inflamed tissue, enhancing the understanding of treatment effects on the human immune response.

• DSS Model

  The DSS model, frequently used to simulate ulcerative colitis, involves administering DSS in the drinking water . This exposure leads to damage to the colonic epithelial cell monolayer, triggering the invasion of bacteria and related antigens into the mucosa, which in turn induces the secretion of human pro-inflammatory cytokines such as IL-6 or TNF-alpha.

• TNBS Model

  The TNBS mouse model initiates colitis via the intra-rectal administration of TNBS, a hapten agent, dissolved in ethanol. This procedure, involving a single TNBS dose, triggers acute inflammation specifically in the distal portion of the colon. The critical role of CD4+ T cells bearing a Th1 profile in the onset of colitis underscores the relevance of this model to human conditions. The mechanism involves ethanol disrupting the epithelial barrier, which facilitates TNBS binding to mucosal proteins. This binding renders the proteins immunogenic, setting them up for processing by antigen-presenting cells in the lamina propria. The subsequent reaction triggers an excessive IL-12 secretion by macrophages, inducing a robust Th1-pro-inflammatory immune response.

• Acute Model

  The acute model of IBD follows a precise schedule. From day 1 to day 7, we introduce DSS solution to the mice’s drinking bottles. The period from day 8 to day 12 serves as a wash-out phase, where we replace the DSS solution with water. The termination of the acute model can be set between days 11 and 13 post-induction, subject to the health status of the animals. Typically, treatments start prior DSS administration.

• Chronic Model

  The protocol for the chronic IBD model involves three distinct cycles of DSS administration, each serving to perpetuate a chronic condition of IBD. The first cycle initiates on Day 1, with subsequent cycles commencing on Days 12 and 23. From Day 1 through Day 27, we provide the animals with the DSS solution in their water bottles. A wash-out period starts from Day 7 and extends to Day 33, during which we substitute the DSS solution with water until the cycle concludes. The chronic model can be terminated between Days 31 and 35, depending on the health of the animals and the client’s specific needs. Typically, treatments start a few days following DSS induction.