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Updated: Apr 18, 2026
A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Generation and analysis of mouse intestinal tumors and organoids harboring APC and K-Ras mutations
1Hubrecht Institute-KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Abstract:
Genetically engineered mouse models of intestinal cancer are experimental systems in which mice are genetically manipulated to develop malignancies in the gastrointestinal tract. These models enable researchers to study the mechanisms of onset, progression, and metastasis of the disease. They also provide a valuable biological system which is suitable for testing (novel) drugs in vivo. Recently, an in vitro culture model has been established in which intestinal epithelial stem cells can grow into three-dimensional, ever-expanding epithelial organoids that retain their original organ identity and genetic stability. This culture system has been applied to diseased epithelia, such as adenoma, adenocarcinoma, and Barrett's epithelium. These organoids can be particularly useful for studying the mechanisms of intestinal tumors and to test (novel) drugs in vitro. Here, we describe our current laboratory protocols to generate and analyze intestinal tumors and organoids harboring APC and K-Ras double mutations.
Insights
Researchers developed lab protocols for genetically engineered mouse models and organoids to study intestinal cancer. These models, featuring APC and K-Ras mutations, aid in understanding tumor development and testing new drugs.
Area of Science:
- Gastroenterology and Oncology
- Cancer Biology
- Translational Research
Background:
- Genetically engineered mouse models (GEMMs) are crucial for studying intestinal cancer mechanisms and drug testing.
- In vitro organoid cultures derived from intestinal epithelial stem cells offer a stable, genetically consistent model system.
- Organoids can mimic diseased epithelia, including adenoma and adenocarcinoma, for research purposes.
Purpose of the Study:
- To outline laboratory protocols for generating and analyzing intestinal tumors in GEMMs.
- To describe methods for creating and analyzing intestinal organoids with specific genetic mutations.
- To facilitate the study of intestinal cancer pathogenesis and therapeutic strategies using these models.
Main Methods:
- Genetic engineering of mice to develop intestinal malignancies.
- In vitro culture of intestinal epithelial stem cells into three-dimensional organoids.
- Generation and analysis of intestinal tumors and organoids harboring APC and K-Ras double mutations.
Main Results:
- Established protocols for generating GEMMs of intestinal cancer.
- Developed methods for culturing and analyzing intestinal organoids with specific mutations.
- Demonstrated the utility of these models for studying intestinal tumor biology.
Conclusions:
- The described protocols provide a robust framework for investigating intestinal cancer.
- These models are valuable for both mechanistic studies and preclinical drug evaluation.
- The combination of GEMMs and organoids enhances the study of gastrointestinal malignancies.
