A mouse model for medulloblastoma and basal cell nevus syndrome.

Medulloblastoma (MB), a tumor of the cerebellum, is the most frequent type of malignant childhood brain tumor. Multiple genes are causally involved in medulloblastoma including PATCHED1 (PTCH). The Patchedl (Ptc1) protein is a receptor for Sonic hedgehog (Shh), a secreted protein ligand. Shh is involved in many signaling processes that control cell fate and growth, among which is its emission from Purkinje cells in the developing cerebellum. Purkinje cell-derived Shh stimulates mitosis of the granule cell precursors that may be the cell type of origin in medulloblastoma. Ptc1 limits the effects of the Shh signal, so mutations in PTCH may lead to persistent granule cell precursors susceptible to further genetic or environmental events that cause medulloblastoma. Mice heterozygous for patched (ptc1) mutations, like heterozygous PTCH humans, have a high rate of medulloblastoma as well as other tumors. We discuss features of the mouse model and how it is contributing to understanding the process of brain tumorigenesis.