Compound Evaluation Services: Inflammatory Bowel Disease (IBD)

Human inflammatory bowel disease (IBD) is a chronic, relapsing and remitting inflammatory condition characterized by two overlapping phenotypes — ulcerative colitis (UC) and Crohn’s disease (CD) — which predominantly affect the colon (UC and CD) and/or the distal small intestine (CD). We offer compound testing in both spontaneous and induced mouse models. The spontaneous model takes advantage of the mucosal inflammation phenotype in the Il-10 deficient C3Bir.129P2(B6) Il10tm1Cgn/Lt (004326) strain whereas the induced models involve exposure to exogenous agents such as dextran sodium sulfate (DSS), trinitrobenzene sulfonic acid (TNBS), or a cell population depleted of regulatory T cells (adoptive transfer model).

JAX® In Vivo Services IBD Capabilities

Leverage the expertise of our PhD-level scientists to help identify compound efficacy. Our In Vivo Services group can design treatment regimens customized to suit the model and compound of interest. Compounds can be administered by the dosing route of your choice, and IBD progression evaluated by clinical symptoms and bowel histopathology.

Modeling Human IBD
  Human Crohn’s Disease Human Ulcerative Colitis Mouse
DSS		 Mouse
TNBS		 Mouse
Il10 -/-		 Mouse CD45RBHI Adoptive Transfer
Areas of Involvement
  • Illeum
  • Cecum
  • Colon
  • Colon
  • Rectum
  • Colon
  • Cecum
  • Distal colon
  • Colon
  • Rectum
  • Cecum
  • Colon
Histology
  • Transmural inflammation
  • Ulceration
  • Submucosal fibrosis
  • Mucosal inflammation
  • Ulceration
  • Loss of Goblet cells
  • Crypt abscesses
  • Mucosal inflammation
  • Ulceration
  • Wound healing,
    fibrosis, mucosal hyperplasia
  • Crypt abscesses
  • Transmural necrosis
  • Acute necrosis and inflammation
  • Mucosal inflammation
  • Ulceration
  • Wound healing, fibrosis, mucosal hyperplasia
  • Wound healing, fibrosis, mucosal hyperplasia

Image of normal proximal colon Image of DSS treated colon
Selected images from H&E stained slides from the proximal segment of formalin-fixed colons. These images were taken from the same region of the proximal colon at 100X magnification. Inflammation, crypt abscesses, and hyperplasia are evident in DSS-treated mice.

Comparison of IBD Study Protocols
  Mouse DSS Mouse TNBS Mouse Il10 -/- Mouse CD45RBHI Adoptive Transfer
Model Acute or Chronic Acute Chronic Chronic
Study
Duration		 3 weeks or 5 weeks 2.5 weeks 2 to 5 months 2 to 5 months
Example protocol
  • Male C57BL/6J at 7-8 weeks of age
  • 1-3 cycles DSS
  • Natural flora transfer
  • Assess prophylactic or therapeutic efficacy
  • Body weight measurement
  • In vivo severity scoring
  • Histology
  • Male BALB/cJ at 7-10 weeks of age
  • Natural flora transfer
  • Assess prophylactic or therapeutic efficacy
  • Body weight measurement
  • In vivo severity scoring
  • Histology
  • Male at 4 or 12 weeks of age
  • Genetic model
  • Natural flora positive
  • Assess prophylactic or therapeutic efficacy
  • Histology 
  • Female Prkcdscid at 6-7 weeks of age
  • CD+ CD45RBHI T-cell transfer
  • Natural flora transfer
  • Assess prophylactic or therapeutic efficacy
  • Body weight measurement
  • In vivo severity scoring
  • Histology

Example Study Design: CD45RBHI Adoptive Transfer Model

timeline of example study design

Experimental Methods: Dosing by all commonly used routes including:

• per os (p.o., gavage) • intrarectal (i.r.)
• intraveous (i.v.) • subcutaneous (s.c.)
• intramuscular (i.m.) • food/water
• intraperitoneal (i.p.) • osmotic pump

Deliverables

  • Blood (serum or plasma)
  • Histology blocks and slides
  • Written report providing the following information:
    • Body weights changes
    • Clinical scoring of IBD symptom severity
    • Colon lengths and weights
    • Histopathology scoring of colon

Standard protocols

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