FIND YOUR MODEL
INFLAMMATORY BOWEL DISEASE
Inflammatory bowel disease (IBD) is a group of inammatory conditions of the gastrointestinal tract with rising incidence worldwide. The main forms of IBD are Crohn's disease and ulcerative colitis, chronic relapsing diseases for which there is still no cure. IBD patients suffer from abdominal pain, rectal bleeding, diarrhea, and weight loss. Histopathological signs include leukocyte inltration, pronounced epithelial hyperplasia, depletion of mucin secreting goblet cells and finally ulceration. Although the etiology of IBD is not completely understood, it has become clear that genetic, microbial, and environmental factors all play a role.
SIA's induced mouse models of acute and chronic intestinal inflammation are invaluable tools for the preclinical evaluation of drug candidates for IBD.
Therapeutic agents can be tested during varying periods from disease induction to
determine prophylactic and therapeutic efficacy.
Readout parameters are body weight, stool consistency and fecal bleeding determined visually or by occult blood detection kits. Additionally, samples can be
isolated for further analyses including histology, serum and tissue biomarker analyses, gene expression and more. Please refer to our In-Vitro services section for more information on ex-vivo studies oered by SIA.
DSS-INDUCED IBD, ACUTE OR CHRONIC
DSS-induced colitis is commonly used to address the pathogenesis of IBD as well as to test efficacy of therapies. Dextran Sulfate Sodium (DSS) is a chemical agent and it’s consumption by animals induces IBD resembling human ulcerative colitis.
Providingmice for several days with DSS polymers in the drinking water induces a very reproducible acute colitis characterized by bloody diarrhea, ulcerations and inflammatory inltration of the colon, due to the DSS toxicity on gut epithelial cells and modulation of the mucosal barrier. This model is particularly useful to target innate immune mechanism of intestinal inflammation.
Chronic DSS colitis is induced by repetitive cycles of oral administration of DSS in drinking water followed by no-DSS. The length of acute DSS-induced IBD study is 10-14 days. The length of chronic DSS-induced IBD study is 8-10 weeks. The study design is dictated by individual experimental needs.
Rectal administration of Oxazolone dissolved in ethanol induces severe colitis in rats or mice, and constitutes an animal model of ulcerative colitis with a characteristic Th2-dependent immune response. The disease is characterized by weight reduction, diarrhea and marked loss of goblet cells. The duration of Oxazolone-induced IBD study is 5-10 days.
T-Cell -Induced IBD
Adaptive transfer of CD4+CD45RBhigh T cells (naive T cells) from healthy wild-type mice into syngeneic recipients that lack T and B cells induces the development of a chronic, progressive colitis and wasting disease sharing common features with both Crohn's disease and ulcerative colitis. The symptoms include chronic, progressive disease with diarrhea and weight loss, heavily inflamed colon, loss of mucus from goblet cells, Th1/Th17 dominated cytokine profile as found in Crohn's disease (IFN-γ, TNF-α, and IL-23). Typical study duration is approximately 30 days.
TNBS colitis is induced by intra-rectal instillation of the haptenizing substance TNBS in ethanol. This model resembles Crohn's disease because of the resulting mucosal inflammation mediated by a T helper type-1 response, with excessive pro-inflammatory cytokine production (IFN-γ TNF-α). The symptoms of the disease include weight loss, diarrhea and bleeding. The length of TNBS-induced IBD study is 5-10 days.
IL-10-DEFICIENT MOUSE MODEL OF IBD
IL-10–/– mice develop spontaneous intestinal inflammation characterized by discontinuous transmural lesions affecting the small and large intestine and by dysregulated production of pro-inflammatory cytokines. Chronic enterocolitis in IL-10–/– mice is mediated by aberrant Th1 responses. This model reflects the chronic aspects of intestinal inflammation and has the advantage of evaluating the effect of prolonged prophylactic or therapeutic treatment of chronic colitis. Study duration depends on individual experiment needs and can vary between 4-8 weeks.