Modeling gliomagenesis with somatic cell gene transfer using retroviral vectors.

Modeling brain tumor formation in experimental animals with somatic cell gene transfer has a long history. In the early experiments naturally occurring retroviruses were used to induce primary brain tumors in a variety of test animals. The subsequent identification of the v-srconcogene within RSV and other cellular proto-oncogenes encoded by other retroviruses moved the field of oncology into the molecular age. Recombinant retroviruses were originally used to infect cells in vitro followed by transplantation. Since then, retroviral vectors have been used to generate glioma formation in vivo via intracerebral injection of neonatal mice. In the most recent models, primary brain tumors can be induced by injecting avian recombinant retroviruses containing different oncogenes, individually or in combination, into transgenic mice genetically engineered for susceptibility to retroviral gene transfer targeting specific cell types in the brain. Animal modeling experiments have contributed substantially to the understanding of the etiology leading to gliomagenesis. The current models provide tumors, which are genetically and histologically similar to their human counterparts, making them attractive to use in drug discovery for treatment of gliomas.