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Updated: Jun 26, 2026
Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma
Published on: February 22, 2015
De novo induction of genetically engineered brain tumors in mice using plasmid DNA
Stephen M Wiesner1, Stacy A Decker, Jon D Larson
1Departments of Pediatrics, Center for Allied Health Programs, Laboratory Medicine and Pathology, and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Abstract:
Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required to generate spontaneous models of glioma, a lethal brain tumor, because nonviral gene transfer is typically transient. To overcome this constraint, we used the Sleeping Beauty transposable element to achieve chromosomal integration of human oncogenes into endogenous brain cells of immunocompetent mice. Genetically engineered, spontaneous brain tumors were induced with plasmid DNA in a matter of weeks in three separate mouse strains. The phenotype of tumors was influenced by the combination of oncogenes delivered, resembling human astrocytoma or glioblastoma in the majority of cases. At least five different genes can be cotransfected simultaneously including reporters, allowing measurement of tumor viability by in vivo imaging. This model can accelerate brain tumor research in a variety of ways such as generation of "humanized" models for high throughput drug screening and candidate gene validation with exceptional speed and flexibility.
Insights
Researchers developed a novel method for creating spontaneous brain tumor models in mice using the Sleeping Beauty transposable element. This technique enables rapid generation of genetically engineered gliomas for accelerated cancer research and drug discovery.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Spontaneous mouse cancer models offer improved human disease recapitulation and clinical efficacy prediction.
- Generating spontaneous glioma models traditionally requires transgenic mice or viral vectors due to transient nonviral gene transfer.
- Existing methods face limitations in speed and flexibility for brain tumor research.
Purpose of the Study:
- To establish a nonviral, efficient method for generating spontaneous glioma models in immunocompetent mice.
- To overcome the transient nature of nonviral gene transfer for creating stable, genetically engineered brain tumors.
- To develop a versatile platform for accelerated brain tumor research, including drug screening and gene validation.
Main Methods:
- Utilized the Sleeping Beauty transposable element for chromosomal integration of human oncogenes into endogenous brain cells.
- Induced genetically engineered, spontaneous brain tumors using plasmid DNA in three different mouse strains.
- Co-transfected up to five genes simultaneously, including reporter genes for in vivo imaging.
Main Results:
- Successfully generated spontaneous brain tumors in weeks across multiple mouse strains.
- Tumor phenotypes varied based on oncogene combinations, resembling human astrocytoma and glioblastoma.
- Demonstrated the ability to measure tumor viability using in vivo imaging via reporter genes.
Conclusions:
- The Sleeping Beauty system provides a rapid and flexible method for creating spontaneous glioma models.
- This approach overcomes previous limitations associated with nonviral gene transfer in generating stable brain tumor models.
- The developed model accelerates research by enabling "humanized" models for high-throughput drug screening and candidate gene validation.
