Authors
Tomotoshi Marumoto, Dinorah Friedmann-Morvinski, Meng Yang, Robert Hoffman, and Inder Verma
Summary
Glioblastomas (GBMs) are highly malignant because of their high mitotic activity and prominent invasive characteristic. Animal models are very essential in order to understand the biology of the disease and to find and validate new therapies. Various animal models for GBMs have been reported so far, however each model has strengths and drawbacks. The transplantation of cultured tumor cells (xenograft or allograft models), often in the immunodeficient recipient animals have been used to model gliomas. While these models are highly reproducible, they do not recapitulate the infiltrative characteristics of glioma, a major cause of lethality 1. Another glioma model in rodents can be generated by treatment with mutagens and histologically resemble gliomas, but the identities of their unique genetic mutations are hard to determine 2. Transgenic models which express oncogenes from a cell/tissue-type specific promoter and knock-out models that lack tumor suppressors are often used for modeling glioma in mice 3,4. These models can induce the genetic alterations leading to tumor formation, but these tumors often arise as a result of secondary mutations, possibly caused by the original alterations during the mouse development 2. Few animal model systems exist for GBM that can reproduce the accumulating somatic mutations in a single cell or a small number of cells surrounded by normal cells. We have reported a mouse GBM model that can recapitulate the pathophysiology of GBM in humans. We utilized the injection of Cre-loxP controlled lentiviral vectors (Tomo LVs) that are able to transduce the activated form of oncogenes in both dividing (such as neural-progenitor cells) and rarely dividing post mitotic cells (such as terminally differentiated astrocytes) in a cell type and a region specific manner in an adult mouse brain 5. We describe here the steps in detail to perform cell-type/region specific injection of Cre-loxP controlled lentiviral vectors in the brain of adult mice.Further details
The protocol was published on Protocol Exchange in 2008. To see the entire protocol, click on the source link.Advertisement
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