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Journal of Neuroscience, Vol 14, 3533-3539, Copyright © 1994 by Society for Neuroscience

ARTICLE

Hypomyelinating peripheral neuropathies and schwannomas in transgenic mice expressing SV40 T-antigen

A Messing, RR Behringer, L Wrabetz, JP Hammang, G Lemke, RD Palmiter and RL Brinster
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706.

We have prepared transgenic mice carrying a temperature-sensitive mutant of the SV40 oncogene (tsA-1609) under the control of 5' flanking sequences from the Schwann cell-specific P0 gene. Four of six founder mice showed moderate to severe hypomyelination in peripheral nerves of tail biopsies, with only rare myelinated fibers. Offspring were obtained from three of these founders. Northern blot and immunohistochemical analyses showed that expression of T-antigen was restricted to the PNS. Mice expressing the highest levels of T-antigen exhibited the most severe hypomyelination. Mice expressing lower levels developed transient mild hypomyelination, but after long latencies developed sporadic schwannomas. An immortalized cell line exhibiting properties of Schwann cells at an arrested stage of differentiation, termed "SCT-1," was derived from one of these tumors.


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