De novo induction of genetically engineered brain tumors in mice using plasmid DNA.
De novo induction of genetically engineered brain tumors in mice using plasmid DNA.
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DOI：
10.1158/0008-5472.can-08-1800
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发表时间：
2009-01-15
期刊：
影响因子：
11.2
通讯作者：
Ohlfest JR
中科院分区：
文献类型：
--
作者：
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
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 co-transfected 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.
