Customized Genetically Engineered Models of IBD

To date, more than 74 types of genetically engineered mouse strains that spontaneously develop colitis and/or ileitis have been reported. 74 genetically engineered mouse models of inflammatory bowel disease (IBD) are further classified into four groups; colitis models, ileitis models, enterocolitis models developing colitis and ileitis, and systemic model developing inflammation in multiple organs including intestine. Overexpression and deficiency of specific genes in animal models could provide insight into specific functions and mechanisms of interesting substances in intestinal inflammation and fibrosis. In addition, pathogenic or regulatory factors during the development of chronic colitis can be studied in genetically engineered mouse models.

Fig. 1. Genetically engineered mouse models of IBD. (Mizoguchi et al., 2016)

Our Genetically Engineered Models

Ace Therapeutics' team of experts has extensive experience in the development of genetically engineered animal models and IBD research, providing clients with high-quality genetically engineered mouse models to aid in IBD pathogenesis research and the development of new therapies.

We conduct gene deletion and inversion or complete inactivation by the Cre-lox recombination system. Furthermore, we use technologies such as reversibly controlling expression, overexpressing by introducing genes of interest in all cells or specific types of cells, and interfering with overexpressed non-functional proteins with a target factor, to create genetically engineered mouse models. These technologies allow us to help clients analyze the effect of genes on the development of colitis.

IL-10 Knockout Models

IL-10 is a regulatory cytokine that plays a key role in immunosuppression and inflammation. We can create genetically engineered IL-10 knockout mice that spontaneously develop intestinal inflammation after 3 months of age. This model allows us to help our clients understand IBD-related microbiota-host interactions, and conduct studies targeting gut bacteria and probiotics.

Specific Genetically Engineered Mouse Models

We also design and develop specific genetically engineered mouse models based on clients' needs, such as Mdr1a knockout model. Through large scale, individual and collaborative genome wide association scanning studies, we help our clients to appropriately select genotypic factors that influence epithelial barrier function, T and/or B cell regulation, and inflammatory signaling.

Preclinical Evaluation in Genetically Engineered Models of IBD

We provide meticulous experimental design, comprehensive phenotyping, and careful data interpretation to evaluate transgenic mouse models of IBD and test the efficacy of potential therapies.

Standard Readings

• Percentage change in body weight
• Disease Activity Index: Diarrhea and blood in stool score
• Fecal LCN2 and Calcineurin
• Terminal colon weight and length measurements
• Terminal histopathology and/or IHC analysis

Additional Readings

• Endoscopy: Colitis severity and stool consistency score
• Colon cytokines
• Colonic Myeloperoxidase (MPO)
• Fecal MPO
• Peripheral lymphoid organs immunophenotype
• Intestinal lamina propria immunophenotype
• Genetic testing: Confirm the success of the transgenic modification by detecting the expression or deletion of the target gene.
• Customized testing

Ace Therapeutics offers a combination of methods to help clients comprehensively evaluate the efficacy and applicability of transgenic mouse models in mimicking IBD, providing important experimental data and insights for further study of disease mechanisms, discovery of new therapeutic targets, and evaluation of the efficacy of therapeutic approaches. Contact us to learn more.