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Updated: Apr 14, 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
Development of a novel mouse glioma model using lentiviral vectors
Tomotoshi Marumoto1, Ayumu Tashiro, Dinorah Friedmann-Morvinski
1Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Abstract:
We report the development of a new method to induce glioblastoma multiforme in adult immunocompetent mice by injecting Cre-loxP-controlled lentiviral vectors expressing oncogenes. Cell type- or region-specific expression of activated forms of the oncoproteins Harvey-Ras and AKT in fewer than 60 glial fibrillary acidic protein-positive cells in the hippocampus, subventricular zone or cortex of mice heterozygous for the gene encoding the tumor suppressor Tp53 were tested. Mice developed glioblastoma multiforme when transduced either in the subventricular zone or the hippocampus. However, tumors were rarely detected when the mice were transduced in the cortex. Transplantation of brain tumor cells into naive recipient mouse brain resulted in the formation of glioblastoma multiforme-like tumors, which contained CD133(+) cells, formed tumorspheres and could differentiate into neurons and astrocytes. We suggest that the use of Cre-loxP-controlled lentiviral vectors is a novel way to generate a mouse glioblastoma multiforme model in a region- and cell type-specific manner in adult mice.
Insights
Researchers developed a novel method to create glioblastoma multiforme models in mice using lentiviral vectors. This technique allows for precise, cell-type-specific induction of brain tumors in adult animals.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options.
- Accurate preclinical models are crucial for understanding GBM pathogenesis and developing new therapies.
Purpose of the Study:
- To develop a novel, region- and cell type-specific method for inducing glioblastoma multiforme in adult immunocompetent mice.
- To utilize Cre-loxP-controlled lentiviral vectors for targeted oncogene expression.
Main Methods:
- Injection of Cre-loxP-controlled lentiviral vectors expressing Harvey-Ras and AKT oncogenes into specific brain regions (hippocampus, subventricular zone, cortex) of mice heterozygous for Tp53.
- Analysis of tumor formation, characterization of tumor cells (CD133 expression, tumorsphere formation, differentiation potential).
Main Results:
- Glioblastoma multiforme was successfully induced in the subventricular zone and hippocampus, but rarely in the cortex.
- Transplanted tumor cells formed glioblastoma multiforme-like tumors with stem cell markers (CD133+) and differentiation capacity.
- The method allows for cell type- and region-specific tumor induction.
Conclusions:
- Cre-loxP-controlled lentiviral vectors provide a novel and effective tool for generating region- and cell type-specific mouse models of glioblastoma multiforme.
- These models can recapitulate key features of human GBM, including stem cell properties and differentiation.
- This approach facilitates the study of GBM in a more controlled and relevant preclinical setting.
