Mechanism of demyelination in DM20 transgenic mice involves increased fatty acylation
| Autor: | Baldwin C. Mak, Lawrence Fisher, Mario A. Moscarello, Nancy Barrese |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Genetically modified mouse
chemistry.chemical_classification medicine.medical_specialty Proteolipid protein 1 Proteolipids Transgene Fatty acid Cellular and Molecular Neuroscience Myelin medicine.anatomical_structure Endocrinology chemistry Biochemistry Internal medicine Glycine medicine Fatty acylation |
| Zdroj: | Journal of Neuroscience Research. 53:143-152 |
| ISSN: | 1097-4547 0360-4012 |
| Popis: | Transgenic mice (ND4) containing 70 copies of the transgene encoding DM20 were clinically normal up to 3 months of age, spontaneously demyelinated there-after and died in 8-10 months. Whereas the myelin fraction from normal mice increased in amount from 1-4 months as expected, the corresponding fraction in ND4 mice remained constant over this period. In order to study the mechanism by which decreased myelin synthesis was manifest in the ND4 mouse, we investigated the amounts of proteolipids at various ages. The amount of proteolipid protein (PLP) was greatly decreased after 1-2 months in the ND4 mice. Although the message for DM20 was increased (transgene mRNA), very little DM20 was found in myelin at 1 month. It subsequently increased so that at 3-4 months the amount of DM20 in myelin isolated from transgenic animals was much higher than in normal mice. Characterization of the DM20 and PLP at 1 month of age showed that the amount of fatty acid (stearate and palmitate) was increased and the N-terminal glycine was methylated. These data suggested that high copy numbers of the cDNA for DM20 affected post translational events which we postulate affected the proper insertion of both DM20 and PLP in the myelin bilayer. |
| Databáze: | OpenAIRE |
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