[Analysis of S100beta-v-erbB transgenic rats prone to brain tumors]

We established a line of transgenic rats expressing v-erbB, the viral form of EGFR, under the transcriptional regulation of the S100beta promoter. This is the first transgenic rat model that spontaneously develops brain tumors. The rats maintained under conventional housing conditions until the occurrence of severe neurological symptoms or death. Of the 54 rats analyzed, 52 (96%) developed brain tumors. Histopathologically, they were classified into four subtypes: glioblastoma-like malignant glioma, anaplastic oligodendroglioma, low-grade oligodendroglioma, and low-grade astrocytoma. Eleven transgenic rats developed two different histological types of brain tumor, which were considered to be of multiclonal origin, because of the lack of mutual histological transitions. Almost all brain tumors contained neoplastic cells immunoreactive for S100 and GFAP. Diffuse immunoreactivity for Olig2 and Nkx2.2 was observed in neoplastic cells in all oligodendroglial tumors, but not in the malignant gliomas. Electron microscopy revealed the presence of intermediate filament bundles devoid of side arms, indicating glial differentiation. There was no evidence of cilia, microvilli, cell junction, neurosecretory granules, synaptic structures, or neurofilaments, excluding the possibility of ependymal or neuronal tumors. Reproducible development of particular histologic types of brain tumors in unique localizations might be useful for further study on the histogenesis and molecular mechanisms of development of glial tumors due to disruption of the EGFR pathway.