Ulcerative Colitis Animal Model Service

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Ulcerative Colitis Animal Model Service

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Protheragen has advanced, bespoke research solutions in rare gastrointestinal disorders research and focuses on comprehensive, high-quality, end-to-end animal model development. Our platform targets ulcerative colitis, providing dependable and relevant in vivo models for researchers working on innovative therapeutic strategies. From model selection, customization, detailed phenotypic characterization, and through to final data delivery, we serve as a reliable partner of your R&D team, providing reliable and reproducible preclinical data.

Introduction to Ulcerative Colitis Animal Models

Animal models of ulcerative colitis serve to understand the disease's mechanisms and test possible therapeutics. These models aim to replicate features of colonic mucosal inflammation, mucosal epithelium destruction, crypt abscesses, and infiltrating inflammatory cells. A key aim is to develop a reliable in vivo system that captures the characteristics of ulcerative colitis, thereby enabling critical investigations into mechanisms of action, biodistribution, efficacy, and safety of candidate compounds. A rigorously developed model is the basis of translational research, bridging the gap between in vitro findings and human trials.

CD45RBhighCD4+ T cell adoptive transfer model.Fig.1 CD45RBhighCD4+ T cell adoptive transfer scheme. (Katsandegwaza, B., et al., 2022)

Methods of Ulcerative Colitis Animal Model Development

A spectrum of well-established methodologies is employed to induce ulcerative colitis-like pathology in animals, each offering distinct advantages for specific research objectives.

  • Chemical-Induced Method
    The chemical induction approach establishes colitis models by administering a specific chemical agent, typically via oral gavage or rectal instillation. This method reliably elicits acute or chronic intestinal inflammation and characterizes mucosal injury.
  • Adoptive T-Cell Transfer
    This model involves the isolation and transfer of naive CD45RBhighCD4+ T-cells into immunodeficient recipients. The procedure drives a progressive, T-cell-mediated colitis that closely recapitulates chronic intestinal immune dysregulation.
  • Genetically Engineered Method
    Genetically engineered models, such as IL-10-deficient mice, develop spontaneous colitis due to a loss of immunological tolerance, providing critical insights into the pathogenesis of genetically predisposed forms of inflammatory bowel disease.

Our Services

Harnessing advanced technology along with a dedicated team, Protheragen provides ulcerative colitis model development service built on a service scientific foundation, a broad scope of customization, and a promise of high-quality data integrity. We excel by integrating proven protocols with comprehensive analyses to ensure each model is not just created, but fully validated to meet the precise mechanistic and therapeutic questions of your specific research program. This greatly mitigates the risks in drug development and offers a dependable route from observation in the preclinical stage to practical use of the therapy.

Animal Models of Ulcerative Colitis

Genetically Engineered Models

Leveraging expertise in genetic engineering, we create precise animal models that replicate the key molecular and phenotypic features of ulcerative colitis.

  • IL-10 Knockout Model
  • Others

Induced Models

Utilizing precisely protocols with agents such as dextran sulfate sodium (DSS), trinitrobenzene sulfonic acid (TNBS), or oxazolone to induce a range of acute, chronic, and relapsing colitis phenotypes for therapeutic investigation.

  • TNBS-Induced Model
  • DSS-Induced Model
  • Oxazolone-Induced Model
  • Others

T Cell Transfer Models

Transfer of naive CD45RBhighCD4+ T cells from wild-type or genetically modified donor mice into immunodeficient recipients (SCID or Rag-knock-out mice) results in progressive colitis, providing a robust platform for evaluating T-cell-specific mechanisms.

Rag2-KO Mouse for Ulcerative Colitis Research

Model Name Rag2-KO Mouse
Model Type Genetically Engineered Mouse Model (GEMM)
Modeling Method Knockout
Targeted Disease Ulcerative Colitis; Severe Combined Immunodeficiency; Immunodeficient
Sales Status Repository Live
Detailed Description Rag2 knockout mice were generated by targeting a partial deletion of exon 3, resulting in a frameshift mutation and consequent loss of gene function.
Applications & Therapeutic Areas Employing Rag2-KO mice as immunodeficient hosts for adoptive T-cell transfer studies enables the investigation of T-cell-driven chronic colitis in a controlled environment.

Case Study: Oxazolone-Induced Ulcerative Colitis Rat Model

Model Introduction

Utilizing Sprague-Dawley rats, the oxazolone-induced ulcerative colitis model replicates key features of human inflammatory bowel disease, including colonic mucosal injury, immune dysregulation, and systemic inflammatory responses. Characterized by robust phenotypic and molecular consistency with human ulcerative colitis pathology, this model serves as a validated platform for evaluating novel therapeutics.

Methodology

  • Animal Model: Sensitization was performed by topical application of 0.15 mL oxazolone (40 mg/mL in anhydrous ethanol) on shaved dorsal skin for 7 days. Following a 24-hour fast, colitis was induced via intrarectal administration of 0.5 mL oxazolone (10 mg/mL in 50% ethanol/water). The control group underwent the same procedures, with 0.15 mL of anhydrous ethanol topically applied to the shaved dorsal region and 0.5 mL of 0.9% saline administered intrarectally.
  • Phenotypic Analysis Methods
    • Macroscopic Evaluation: Following dissection, colonic tissues were cleared of mesentery and adipose tissue on ice, then dissected longitudinally along the mesenteric border. After rinsing with ice-cold saline, colon length and weight were measured to determine the weight-to-length ratio.
    • Histological Assessment of Colitis: Colon segments were fixed in 4% paraformaldehyde, embedded in paraffin. Tissue sections were stained with hematoxylin and eosin (HE) for standardized assessment of inflammatory infiltration and mucosal damage.
    • Serum Biomarker Quantification: Blood was collected from the abdominal aorta, and serum was isolated by centrifugation at 3,500 rpm for 10 minutes. iNOS, tNOS, IL-13, IL-4, and IL-10 levels were measured using ELISA kits.

Phenotypic Analysis & Results

Colitis severity was assessed using colon length and the colon weight-to-length ratio. Oxazolone-induced colitis resulted in both shortened colons and an increased colon weight-to-length ratio, as shown in Fig.2A and 2B. Histological assessment identified severe epithelial injury, marked by goblet cell loss and crypt destruction. As illustrated in Fig.2C and 2D, the model group significantly elevated the serum levels of iNOS and tNOS compared to the control group. Fig.2E and 2F demonstrated that, compared to the control group, the proinflammatory marker IL-13 was elevated in the serum of the model group, while the anti-inflammatory markers IL-4 and IL-10 were decreased.

Evaluation of the oxazolone-induced colitis model.Fig.2 Characterization of oxazolone-induced colitis model. Colon length (A) and the colon weight/length ratio (B) were determined. The expression levels of iNOS, tNOS, IL-4, and IL-10 in serum (C-F) were measured by ELISA analysis. Data are presented as mean ± SEM (n=5; *p < 0.05, **p < 0.01).

Conclusion

Research involving oxazolone-induced ulcerative colitis models using Sprague-Dawley rats effectively replicates the key histopathological and immunopathological features of human ulcerative colitis, which include mucosal inflammation and impaired cytokine and repair mechanisms. The model's ability to demonstrate reliability in macroscopic, histological, and serological evaluations provides an in vivo system for evaluating potential anti-inflammatory therapies for ulcerative colitis.

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Protheragen's developed and characterized animal model service is essential for advancing preclinical research by providing the in vivo context for detailed assessments in pharmacodynamics and pharmacokinetics, as well as toxicology evaluations. Collaborating with us means obtaining expertise and technology that results in more reliable and predictive data that quickens the transition of potential therapies from the laboratory to the bedside. Should you require further details or a quotation for our animal model development services, we invite you to get in touch.

Reference

  • Katsandegwaza, Brunette et al. "Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease." International journal of molecular sciences 23.16 (2022): 9344.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.