Project name: Mus musculus

Description: To determine the regulatory pathways necessary for astrocytoma formation within complex adult brain microenvironments, we engineered mice for adult astrocyte-specific disruption of key regulators (pRb, Kras and Pten). Drivers of all astrocytoma grades were identified using CreERTM-inducible alleles. Inactivation of pRb was necessary to initiate grade II disease, and was the only lesion to do so. Additional activation of Kras progressed disease to grade III, while further Pten inactivation facilitated grade IV (glioblastoma) progression. These outcomes were elicited whether somatic events were induced broadly or focally. In vivo inactivation of pRb, which induced astrocyte proliferation and apoptosis, activated the MAPK pathway, while Kras activation and Pten loss triggered PI3K pathways.TRPhet denotes mice with Inhibition of Rb, Over-expression of Kras and Deletion of one Copy of PTEN; TRPnull denotes mice with Inhibition of Rb, Over-expression of Kras and Deletion of both copies of PTEN; TR denotes mice with Inhibition of Rb, Over-expression of Kras.Overall design: high grade astrocytoma tumors were obtained from tamoxifen induced mice

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2010-12-10