nos2 inactivation promotes the development of medulloblastoma in ptch1+？ mice by deregulation of gap43–dependent granule cell precursor migrationnos2失活促进发展成神经管细胞瘤在ptch1 + 老鼠的放松管制gap43-dependent颗粒细胞前体迁移.pdfVIP

Nos2 Inactivation Promotes the Development of Medulloblastoma in Ptch1+/ 2 Mice by Deregulation of Gap43–Dependent Granule Cell Precursor Migration 1. 2. 2 2 1 1 Daniel Haag , Petra Zipper , Viola Westrich , Daniela Karra , Karin Pfleger , Grischa Toedt , Frederik 1 1 1 3 2 1 Blond , Nicolas Delhomme , Meinhard Hahn , Julia Reifenberger , Guido Reifenberger , Peter Lichter * ¨ 1 Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2 Department of Neuropathology, Heinrich Heine University, Dusseldorf, ¨ Germany, 3 Department of Dermatology, Heinrich Heine University, Dusseldorf, Germany Abstract Medulloblastoma is the most common malignant brain tumor in children. A subset of medulloblastoma originates from granule cell precursors (GCPs) of the developing cerebellum and demonstrates aberrant hedgehog signaling, typically due to inactivating mutations in the receptor PTCH1, a pathomechanism recapitulated in Ptch1+/ 2 mice. As nitric oxide may regulate GCP proliferation and differentiation, we crossed Ptch1+/ 2 mice with mice lacking inducible nitric oxide synthase (Nos2) to investigate a possible influence on tumorigenesis. We observed a two-fold higher medulloblastoma rate in Ptch1+/ 2 Nos22/ 2 mice compared to Ptch1+/ 2 Nos2+/+ mice. To identify the molecular mechanisms underlyin