Aberrant dendrite growth in central nervous system white matter induced by a mutant proteolipid protein transgene

Transgenic mice were produced that carry a construct encoding a mutant form of the DM20 isoform of myelin proteolipid protein. The transgene is under the direction of the human Plp gene promoter, which has previously been shown to direct tissue-specific expression of transgenes. Two lines of mice were generated with this construct, both of which express the transgene at extremely low levels. Central nervous system myelination proceeds normally in the transgenic mice. However, in aged transgenic mice, areas of dendrite processes synapsed with axonal termini were observed within the white matter of the spinal cord. This phenotype was accompanied by focal areas of astrocytic hypertrophy and an increase in apoptotic cell death in white matter but not gray matter. One interpretation of these findings is that expression of the mutant DM20 alters signaling between oligodendrocytes and neurons, producing abnormal neurite outgrowth.