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Induction of neuronal degeneration in transgenic mice expressing ts1-envelope protein in astrocytes is enhanced by wild type MoMuLV


, : Induction of neuronal degeneration in transgenic mice expressing ts1-envelope protein in astrocytes is enhanced by wild type MoMuLV. Society for Neuroscience Abstracts 27(2): 2622

The ts1 mutant of Moloney murine leukemia virus (MoMuLV) infection leads to development of spongiform encephalomyelopathy in FVB/N newborn mice. Neuronal loss occurs in the absence of viral infection in neurons. We hypothesized that virus envelope protein accumulation in astrocytes is responsible for the development of this neurodegenerative disease. To further explore this possibility, we constructed transgenic mouse expressing the ts1-env gene with a GFAP promoter, which express the ts1-env gene only in astrocytes. Our results showed that ts1-env transgenic mice exhibited only mild spongiform changes with neuronal loss at 12 to 18 months old. Expression of the ts1 envelope protein in these mice was also limited. To increase the expression of viral envelope protein, the transgenic mice were infected with wild type (WT) of MoMuLV, which does not cause neurodegenerative disorders. At two month post inoculation these mice showed clinical signs and brain lesions comparable to that of ts1-infected mice. The expression of ts1 mRNA and viral precursor envelope protein was much higher in the WT infected transgenic mice than that of FVB/N mice. However the virus titer is comparable to that of WT infection in FVB/N mice and the phenotype of progeny virus remains that of WT. The results suggest that expression of high level of ts1 envelope protein in astrocytes is sufficient to induce neuronal degeneration of ts1 infection and ts1 envelope protein expression in transgenic mice is enhanced by MoMuLV infection.

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