Tag: Genes Cells & Jaws

Presenter: Anita Kasina, Biology

Malignant gliomas are an aggressive and incurable form of cancer with thousands of new cases annually, many of which result in death within one year. Previously, we identified Oligodendrocyte Precursor Cells (OPCs) as the cell of origin for glioma. We are now examining wild-type (WT) and cancer-prone OPCs on a molecular level to understand the mechanisms by which OPCs form gliomas. Specifically, we are investigating whether brain injury, known to stimulate transient proliferation of WT OPCs, can cause uncontrolled proliferation of mutant OPCs, and ultimately cancer. We inactivated the tumor suppressor genes p53 and NF1 specifically in adult brain OPCs using an OPC-specific gene promoter, NG2, to drive the expression of an inducible form of the DNA recombinase Cre, which is activated by the drug Tamoxifen (TMX). We are currently optimizing TMX delivery to better control the number of mutated cells. We have found that delivering TMX over consecutive days greatly increases the number of mutant OPCs. Mice given 1, 3, 5, and 7 days of TMX had a significant increase in labeling from 1 to 3 and 3 to 5 days but not from 5 to 7 days, indicating 5 days as the ideal maximal dose. We are now quantifying TMX-induced mutagenesis in other brain areas to identify regional differences. Overall, this data provides a solid basis for future experiments using TMX to induce mutations in OPCs, giving us the level of control necessary to understand the differences between WT and mutant OPC proliferation that ultimately cause cancer.