Abstract |
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 approximately 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.
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Authors | R S Johnson, J C Roder, J R Riordan |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 64
Issue 3
Pg. 967-76
(Mar 1995)
ISSN: 0022-3042 [Print] England |
PMID | 7532214
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Myelin Proteins
- Myelin Proteolipid Protein
- Nerve Tissue Proteins
- Plp1 protein, mouse
- RNA, Messenger
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Topics |
- Alternative Splicing
- Animals
- Demyelinating Diseases
(genetics, pathology)
- Female
- Gene Expression
- Male
- Mice
- Mice, Transgenic
- Myelin Proteins
(genetics)
- Myelin Proteolipid Protein
- Myelin Sheath
(metabolism, ultrastructure)
- Nerve Tissue Proteins
- RNA, Messenger
(genetics)
- Transcription, Genetic
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