A mouse prion protein transgene rescues mice deficient for the prion protein gene from Purkinje cell degeneration and demyelination

Disruption of both alleles of the prion protein gene, Pmp, renders mice resistant to prions; in a Prnp(O/O) line reported by some of us, mice progressively developed ataxia and Purkinje cell loss. Here we report torpedo-like axonal swellings associated with residual Purkinje cells in Prnp(O/O) mice, and we demonstrate abnormal myelination in the spinal cord and peripheral nerves in mice from two independently established Prnp(O/O) lines. Mice were successfully rescued from both demyelination and Purkinje cell degeneration by introduction of a transgene encoding wild-type mouse cellular prion protein. These findings suggest that cellular prion protein expression may be necessary to maintain the integrity of the nervous system.