We have created transgenic mice bearing varying copy numbers of a transgene coding for normal DM‐20, the alternatively spliced quantitatively minor isoform of myelin proteolipid protein. Demyelination of the CNS occurs as a consequence of 70 copies of this transgene. Overt symptoms begin at ∼3 months with a wobbling gait. Occasional seizures lasting a few seconds begin at 3–4 months. These symptoms progress in severity with age. Death occurs by 8–10 months. Myelination in 2‐month‐old animals, before the onset of any overt symptoms, appears morphologically normal at the electron microscopic level. However, the myelin in these 2‐month‐old animals has a reduced amount of the major myelin proteolipid protein and about three times as much DM‐20 as normal animals. In 7‐month‐old animals that appear to be undergoing demyelination in the CNS, both the major myelin proteolipid protein and DM‐20 are greatly reduced relative to the 2‐month‐old animal. Mice with 17 copies of the transgene also have a reduced amount of the major myelin proteolipid protein but appear to be otherwise normal and have normal life spans (>2 yr). Mice with low copy numbers of the transgene (2–4 copies) appear to be unaffected and have normal life spans.