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.
Wiesner
Stephen M
SM
Departments of Pediatrics, Center for Allied Health Programs, Laboratory Medicine and Pathology, and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Decker
Stacy A
SA
Larson
Jon D
JD
Ericson
Katya
K
Forster
Colleen
C
Gallardo
Jose L
JL
Long
Chunmei
C
Demorest
Zachary L
ZL
Zamora
Edward A
EA
Low
Walter C
WC
SantaCruz
Karen
K
Largaespada
David A
DA
Ohlfest
John R
JR
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D005818:Genetic Engineering / Q000379:methods; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009857:Oncogenes; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011094:Polyethyleneimine / Q000008:administration & dosage
D011094:Polyethyleneimine; D004247:DNA