跳转至内容
Merck

Interferon-gamma induced medulloblastoma in the developing cerebellum.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2004-11-13)
Wensheng Lin, April Kemper, Ken D McCarthy, Peter Pytel, Jian-Ping Wang, Iain L Campbell, Manuel F Utset, Brian Popko
摘要

We have generated a mouse model system with a high incidence of medulloblastoma, a malignant neoplasm believed to arise from immature precursors of cerebellar granule neurons. These animals ectopically express interferon-gamma (IFN-gamma) in astrocytes in the CNS in a controlled manner, exploiting the tetracycline-controllable system. More than 80% of these mice display severe ataxia and develop cerebellar tumors that express synaptophysin, the mouse atonal homolog MATH1, sonic hedgehog (SHH), and Gli1. IFN-gamma-induced tumorigenesis in these mice is associated with increased expression of SHH, and SHH induction and tumorigenesis are dependent on signal transducer and activator of transcription 1 (STAT1). When IFN-gamma expression is shut down with doxycycline at postnatal day 12 (P12), the clinical symptoms dissipate and the mice do not develop tumors, whereas if transgene expression is shut down at P16, the clinical symptoms and tumors progress to lethality, indicating that IFN-gamma is required for tumor induction but not progression. The tumors that occur in the continued presence of IFN-gamma display extensive necrosis and apoptosis as well as macrophage and lymphocytic infiltration, whereas the tumors that develop in mice in which IFN-gamma expression is shut down at P16 do not. Thus, IFN-gamma expression in the perinatal period can induce SHH expression and medulloblastoma in the cerebellum by a STAT1-dependent mechanism, and its continued presence appears to promote a host response to the tumor.

材料
货号
品牌
产品描述

Sigma-Aldrich
ApopTag Plus原位凋亡荧光素检测试剂盒, The ApopTag Plus Fluorescein In Situ Apoptosis Detection Kit detects apoptotic cells in situ by the indirect TUNEL method, utilizing an anti-digoxigenin antibody that is conjugated to a fluorescein reporter molecule.