title: Development of a novel mouse glioma model using lentiviral vectors.
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.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Tomotoshi
authors.initials: T
authors.lastname: Marumoto
authors.forename: Ayumu
authors.initials: A
authors.lastname: Tashiro
authors.forename: Dinorah
authors.initials: D
authors.lastname: Friedmann-Morvinski
authors.forename: Miriam
authors.initials: M
authors.lastname: Scadeng
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Soda
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D016158:Genes, p53; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006367:HeLa Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008954:Models, Biological