Customized Spontaneous Gene Mutation Models of IBD

Spontaneous gene mutation models of IBD develop from spontaneously occurring mutations rather than from gene overexpression or gene suppression. Commonly used models include SAMP1/YitFc and C3H/HeJBir. Differently from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of these two strains occurs spontaneously, without genetic, chemical or immunological manipulation. In addition, both mice have remarkable similarities to the human condition in terms of disease site, histologic features, incidence of extraintestinal manifestations, and response to conventional therapies. Thus, the spontaneous gene mutation models are particularly suitable for elucidating pathways that precede the clinical phenotype that may lead to preventive, and therefore more efficacious, intervention with the natural course of disease, or alternatively, for the development of therapeutic strategies directed against chronic established ileitis.

Fig. 1. Morphologic and functional epithelial alterations in SAMP mice. (Pizarro et al., 2011)

Our Spontaneous Gene Mutation Models

Ace Therapeutics offers the SAMP1/YitFc and C3H/HeJBir mice models of Crohn's disease (CD)-like ileitis to help clients further understand the role of genetics, mucosal immunity, leukocyte trafficking, cytokine biology, and epithelial barrier function in the pathogenesis of chronic intestinal inflammation and to develop therapeutic strategies for CD.

We provide a one-stop service from model construction to testing the efficacy of novel treatment modalities for chronic intestinal inflammation and IBD. Our experienced team of experts will guide you through the entire process to ensure the reliability of the results.

SAMP1/YitFc Model of Colitis

The SAMP1/YitFc strain develops spontaneous colitis at 10 to 20 weeks of age. In this model, the development and progression of IBD follows a well-defined time course, allowing us to help our clients evaluate new therapies for different disease stages. In addition, the response to anti-TNF therapy in this subline is similar to that of clinical patients, providing validity and translatability in evaluating similar new drugs.

The SAMP1/YitFc model has several characteristics:

• Almost all animals develop chronic ileitis, mice aged 30 to 40 weeks typically develop persistent severe ileitis.
• Affecting the terminal ileum and segmental transmural inflammation, this model resembles CD.
• Perianal fistula and intestinal stricture formation are observed in some mice.

C3H/HeJBir (C3Bir) Model of Colitis

C3H/HeJBir mice develop disease primarily right-sided colitis characterized by acute and chronic inflammation. This strain represents a highly susceptible phenotype for colitis, allowing us to help our clients study the interplay between immune, environmental, and genetic factors that contribute to IBD.

Preclinical Evaluation in Spontaneous Gene Mutation Models

Ace Therapeutics offers a variety of advanced methods to comprehensively assess the representativeness, reliability, and applicability of spontaneous gene mutation models of IBD, supporting further deepening of research into the pathogenesis of IBD.

Identification of Ileitis-Susceptibility Loci

We perform genome-wide scans of populations generated by crossing SAMP1/YitFc mice or C3H/HeJBir mice with other mice to identify ileitis-associated alleles.

• These scans can reveal chromosomal loci that were strongly linked to the presence of inflammatory changes.
• The strongest associations are confirmed through the generation of interval-specific congenic strains.
• Genes contained in each locus are identified through a genetic database search.
• The most suitable regional candidates are selected and further studied by both sequence analysis as well as by expression and functional studies.

Physiological Measurements

Measure body weight changes, fecal characteristics, and intestinal permeability of animals.

Pathogenesis Study of IBD

Analyze the changes of key molecular pathways in the model by immunohistochemistry and Western blot, and to explore how the gene mutation leads to the development of IBD by affecting cell signaling and immune response.

Ace Therapeutics has extensive experience in using SAMP1/YitFc and C3H/HeJBir models to test the efficacy of novel therapeutic modalities for chronic intestinal inflammation and IBD. If you are interested in our services, please contact us today for more information!