HYPOMYELINATING PERIPHERAL NEUROPATHIES AND SCHWANNOMAS IN TRANSGENICMICE EXPRESSING SV40 T-ANTIGEN

We have prepared transgenic mice carrying a temperature-sensitive muta nt of the SV40 oncogene (tsA-1609) under the control of 5' flanking se quences from the Schwann cell-specific P-0 gene. Four of six founder m ice showed moderate to severe hypomyelination in peripheral nerves of tail biopsies, with only rare myelinated fibers. Offspring were obtain ed from three of these founders. Northern blot and immunohistochemical analyses showed that expression of T-antigen was restricted to the PN S. Mice expressing the highest levels of T-antigen exhibited the most severe hypomyelination. Mice expressing lower levels developed transie nt mild hypomyelination, but after long latencies developed sporadic s chwannomas. 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.