New Tumor Mouse Models Using CRE Inducible Lentiviral Vectors

Inventors: Yasushi Soda, Tomotoshi Marumoto, & Inder Verma
Potential Uses: Use of Cre-loxP-controlled lentiviral vectors to generate a mouse cancer model(s) in a region- and cell type-specific manner in adult mice. Such models can be used for drug development & biological analysis of tumor development.

We have developed a mouse using CRE Inducible Lentiviral Vectors to induce cell-specific or region-specific oncogene expression. Our initial work has provided 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 developed. Mice developed glioblastoma multiforme when transduced either in the subventricular zone or the hippocampus. 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. 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. Thes models can be used for drug development and biological analysis of tumor development.