Two groups of transgenic mice harboring the oncogene (T antigen) from SV40 virus have been produced which display distinct patterns of neuropathology. One group develops tumors in the choroid plexus; the second group develops a demyelinating/hypomyelinating peripheral neuropathy. The proposed study will characterize the pathology which develops in these transgenic mice in terms of the expression of the oncogene which was introduced. The developmental time courses of the choroid plexus tumors and the peripheral neuropathy will be studied morphologically and correlated with the temporal pattern of T antigen gene expression in various tissues. The peripheral neuropathy will be characterized by quantitative morphology. T antigen gene expression will be studied by in situ hybridization using cDNA probes to detect T antigen mRNA, and immunohistochemical localization of T antigen protein using polyclonal and monoclonal antibodies. Whether axons and/or Schwann cells are the primary defect in the peripheral neuropathy will be studied in vivo by transplantation of nerve grafts, and in vitro by recombinations of purified populations of neurons and Schwann cells.
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