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Updated: Sep 23, 2025
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Andrew D Tieniber1, Andrew N Hanna1, Kevin Do1
1Department of Surgery, Hospital of the University of Pennsylvania.
Abstract:
Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and is typically driven by a single mutation in the KIT receptor. Across tumor types, numerous mouse models have been developed in order to investigate the next generation of cancer therapies. However, in GIST, most in vivo studies use xenograft mouse models which have inherent limitations. Here, we describe an immunocompetent, genetically engineered mouse model of gastrointestinal stromal tumor harboring a KitV558Δ/+ mutation. In this model, mutant KIT, the oncogene responsible for most GISTs, is driven by its endogenous promoter leading to a GIST which mimics the histological appearance and immune infiltrate seen in human GISTs. Furthermore, this model has been used successfully to investigate both targeted molecular and immune therapies. Here, we describe the breeding and maintenance of a KitV558Δ/+ mouse colony. Additionally, this paper details the treatment and procurement of GIST, draining mesenteric lymph node, and adjacent cecum in KitV558Δ/+ mice, as well as sample preparation for molecular and immunologic analyses.
Insights
A new immunocompetent mouse model for gastrointestinal stromal tumor (GIST) was developed. This model accurately mimics human GIST, aiding research into targeted molecular and immune therapies for this common sarcoma.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Gastrointestinal stromal tumor (GIST) is the most common sarcoma, typically driven by KIT receptor mutations.
- Current in vivo GIST research heavily relies on xenograft models with limitations.
- There is a need for more accurate preclinical models to study GIST therapies.
Purpose of the Study:
- To describe a novel immunocompetent, genetically engineered mouse model for GIST.
- To detail the breeding, maintenance, and sample preparation for this KitV558Δ/+ mouse model.
- To highlight its utility in studying targeted molecular and immune therapies for GIST.
Main Methods:
- Development of a genetically engineered mouse model with a specific Kit mutation (KitV558Δ/+).
- Breeding and maintenance protocols for the KitV558Δ/+ mouse colony.
- Standardized procedures for GIST, lymph node, and cecum procurement and sample preparation for analysis.
Main Results:
- The developed mouse model exhibits a GIST that mirrors the histological appearance and immune infiltrate of human GIST.
- Mutant KIT is driven by its endogenous promoter, closely resembling human GIST oncogenesis.
- The model has been successfully employed in studies investigating targeted molecular and immune-based therapies.
Conclusions:
- The KitV558Δ/+ genetically engineered mouse model provides a valuable platform for GIST research.
- This immunocompetent model overcomes limitations of xenograft models for studying GIST.
- It facilitates the investigation of novel therapeutic strategies, including targeted and immune-based treatments for GIST.
