IBD Mouse Models for Translational Research

Improve the translation of your inflammatory bowel disease research with IBD mouse models and relevant cellular assays from Charles River. Our experts can guide your selection of the appropriate models depending on your therapeutic target, resulting in data that accurately represents human IBD.

IBD mouse models can be separated into three categories: those which are chemically-induced, those which are achieved by adoptive transfer of T cell subsets, and those that develop spontaneously in genetically modified mice (Eg IL-10-/- mice). Your choice of IBD mouse will depend on which cell type your therapy is targeting.

pathology tissue sample demonstrating dextran sulfate sodium (DSS)-induced colitis in an IBD mouse model.

Figure 1: DSS (sextran sulfate Sodium) administration colitis in animals; analysis of tissue shown at peak disease (d7). Positive control: Cyclosporine CsA, attenuates the inflammatory damage in the gut tissue.

Effects of dextran sulfate sodium (DSS)-induced colitis on tissue in IBD mouse models, visualized by flow cytometry.

Figure 2: Flow cytometric analysis of T cell subsets within the lamina propria at d11 (repair phase) in DSS colitis treated BALB/c mice.

  • Adoptive transfer colitis mouse model. T cell-dependent models of IBD are especially relevant for investigating the immunological mechanisms responsible for the induction, perpetuation, and/or regulation of the chronic disease, as well as the role of Treg.
    Adoptive transfer of CD4+CD45RBhigh T cells (naive T cells, depleted of the Treg population) from healthy wild-type (WT) mice into syngeneic recipients that lack T and B cells induces a pancolitis and small bowel inflammation at 5-8 weeks following T cell transfer.
    The adoptive T cell transfer IBD mouse model recapitulates the clinical pathology (colitis and small bowel inflammation) observed in human intestinal inflammatory diseases such as a Crohn's disease and ulcerative colitis.

Support for Your IBD Program

Which IBD model is best for your program? This decision is driven by numerous factors, but our scientists can guide your selection based on your cell type of interest, proposed MoA, and an examination of what your therapy is trying to achieve. Is your therapy intended to limit the inflammatory response? drive a regulatory environment? modulate the microbiota? drive epithelial repair?

When complementary studies are needed to collect more robust data on your compound, we can enhance your IBD research with relevant human immune cell biology assays. For example, if the aim is to target T cells, it may be useful to examine T cell polarization and Treg function. With a full understanding of your therapy, our team can apply their experience with large and small molecules, microbiome, and genetic interventions to help you choose the best model, advise you on the duration of your study, and keep your program moving forward.

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Therapeutic Modalities in IBD

Therapeutic modalities within the gut include anti-inflammatory approaches, small molecules, corticosteroids, and immunosuppressants. Biologics such as antibodies that target key pro-inflammatory cytokines have been employed to down-regulate the immune response. In addition, therapies aimed at repairing the epithelial barrier layer also limit chronic inflammation associated with IBD.

IBD Therapeutic Microbiome Modalities

Image of results from the evaluation of Lactobacillus strains in IBD mouse models, showing all Lactobacillus strains adhered well to the epithelial cells and inhibited adhesion of AIEC after both co-culture and pre-inoculation.

Evaluation of Different Lactobacillus Strains on the Treatment of IBD Mouse Model.

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  • Immune System and Microbiome
    Our increased understanding of the interplay between the immune system, epithelial barrier, and microbiota within the gut has empowered the development of new approaches to regulate inflammation via modulating the composition of the microbiome. Within the gut, maintaining a regulated intact epithelial barrier layer is critical given the relationship between the epithelium, immune system, and microbiome.
    This balance is continuously under assault by behavioral and environmental factors (food, medications, exercise, stress, hygiene, infections). If an assault persists, and multilayer regulatory mechanisms fail to restore the balance, this can result in a microbial imbalance or dysbiosis.

  • Microbiome Dysbiosis
    The dysbiosis associated with diseases like IBD displays metagenomic and metabolomic modification of bacteria within the gut. This raises the potential of predicting IBD status and subtype from gut microbiome multi-omic features. Therapeutic interventions are now being developed to treat dysbiosis in IBD patients, thereby down- regulating the chronic inflammation and enabling epithelial repair. Some of these strategies include faecal microbiota transplant and probiotics.

The Therapeutic Axis of Microbiome, Inflammation, and Immune Response

microbiome, immune system and inflammation models in mice.

Charles River can support your research in this area as illustrated in this case study using the acute and chronic DSS colitis mouse model - disclosure: projects with live therapeutics were sponsored by our partner Servatus.

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Frequently Asked Questions (FAQs) about IBD Mouse Models

  • What is IBD?

    Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory diseases affecting the gastrointestinal (GI) tract. IBDs are classified into two major categories based on location of the GI tract being affected: ulcerative colitis (UC) mostly affects the colon and rectum, while Crohn’s disease (CD) can affect the entire GI tract1.

    (1) Christopher McDowell & al Inflammatory Bowel Disease (IBD) - https://www.ncbi.nlm.nih.gov/books/NBK470312/

  • What is an IBD Mouse Model?

    IBD mouse models are in vivo preclinical models that capture IBD characteristics and pathology features for preclinical research and drug development.

  • Which IBD mouse model should I use to assess the efficacy of my therapeutic?

    The IBD mouse model selection depends on the target of your therapy and stage of disease at which you aim to intervene. For example, some models are innate cell-driven whereas others are driven by T cells. Only some models can resolve; therefore, one can assess repair in these, but not in other models.

  • What endpoints do you measure in your models?

    We measure in-life clinical scores to demonstrate efficacy. Endpoints can include histology, cytokine multiplexing within the colon tissue, flow cytometric analysis of the lamina propria, IEL, draining lymph node and spleen compartments to determine the immune cell subsets present, and characterized expression of effector molecules.

  • Can in vitro assays help with in vivo model selection?

    In vitro assays using primary human blood cells from healthy donors can elucidate mechanism of action if you are modulating cell behavior in the expected way. Assays can be customized to fit your needs, though available assays include T cell assays, dendritic cell and macrophage assays, and neutrophil assays. These can be complex multicellular assays or more simple assays. In addition, epithelial barrier assays can be run with co-culture of anaerobic bacteria and addition of immune cell subsets.

  • What is the microbiome?

    The microbiome is composed of the bacteria, fungi, protozoa, and viruses that live on and inside the human body. Our gut, particularly the large intestine, is colonized by a huge and diverse microbiome. The number of genes in one person’s microbiome is 200 times the number of genes in the human genome2. In addition to engaging in cross-talk, the bacteria in the microbiome regulate our immune system and epithelial barrier layer and help protect against pathogens.

    (2) Andrew B. Shreiner and al. The gut microbiome in health and in disease - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290017/

  • What is a translational drug discovery program?

    Translational research seeks to produce more meaningful, applicable results that directly benefit human health. The goal of translational research is to translate discoveries more quickly and efficiently into clinic. This can be accomplished with disease-relevant models that accurately reflect the human condition.