Technical Report abstract
Nature Medicine 15, 110 - 116 (2008)
Published online: 4 January 2009 | doi:10.1038/nm.1863
Development of a novel mouse glioma model using lentiviral vectors
Tomotoshi Marumoto1,2, Ayumu Tashiro3, Dinorah Friedmann-Morvinski1, Miriam Scadeng4, Yasushi Soda1, Fred H Gage1 & Inder M Verma1
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.
- Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
- Department of Neurosurgery, Kobe Medical Center National Hospital Organization, 3-1-1 Nishiochiai, Suma-ku, Kobe 654-0155, Japan.
- Kavli Institute for Systems Neuroscience and Center for the Biology of Memory Norwegian University of Science and Technology, Medical Technical Research Center, Trondheim NO-7489, Norway.
- University of California, San Diego Center for Functional Magnetic Resonance Imaging, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Correspondence to: Inder M Verma1 e-mail: verma@salk.edu
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