Progressive paralysis associated with diffuse astrocyte anaplasia in Delta-202 mice homozygous for a transgene encoding the SV40 T antigen

A convenient transgenic astrocytoma model in delta 202 mice, homozygous for a construct encoding the early region of the SV40 virus genome, is described. In the offspring of crosses between delta 202 mice heterozygous for the transgene nearly 60% were transgenic; one third of these developed progressive paralysis starting in the hindlimbs at approximately 35 days of age and died at 90 ± 30 days of age. In affected mice proliferating-non-neuronal cells immunostained with antibodies to the GFAP, an astrocyte marker, whose number increased with age were found in the white matter of the brain, cerebellum and spinal cord, and progressive degeneration and necrosis of spinal motoneurons was observed that may explain the paralysis. The early onset and reproducible time course of the neurological disease suggest that homozygous delta 202 mice, whose proliferating astrocytes appear to damage spinal motoneurons, are a useful model to study astrocyte differentiation, function and tumorigenesis