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De novo induction of genetically engineered brain tumors in mice using plasmid DNA.

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.

Pubmed ID: 19147555


  • Wiesner SM
  • Decker SA
  • Larson JD
  • Ericson K
  • Forster C
  • Gallardo JL
  • Long C
  • Demorest ZL
  • Zamora EA
  • Low WC
  • SantaCruz K
  • Largaespada DA
  • Ohlfest JR


Cancer research

Publication Data

January 15, 2009

Associated Grants

  • Agency: NINDS NIH HHS, Id: 1R21-NS055738-01A2
  • Agency: NCI NIH HHS, Id: R01 CA160782
  • Agency: NCI NIH HHS, Id: R01CA113636-01A1
  • Agency: NINDS NIH HHS, Id: R21 NS055738
  • Agency: NINDS NIH HHS, Id: R21 NS055738-01A2
  • Agency: NIDA NIH HHS, Id: T32DA022616

Mesh Terms

  • Animals
  • Brain Neoplasms
  • DNA
  • Disease Models, Animal
  • Female
  • Genes, Reporter
  • Genes, Tumor Suppressor
  • Genetic Engineering
  • Glioma
  • Injections, Intraventricular
  • Male
  • Mice
  • Oncogenes
  • Plasmids
  • Polyethyleneimine