Late Onset Neuropathy with Spontaneous Clinical Remission in Mice Lacking the POZ Domain of the Transcription Factor Myc-interacting Zinc Finger Protein 1 (Miz1) in Schwann Cells
| Autor: | Hans-Peter Elsässer, Axel Niemann, David Fuhrmann, Herbert Reingruber, Armin Zankel, Adrián Sanz-Moreno, Lara Kern, Dies Meijer |
|---|---|
| Přispěvatelé: | Molecular Genetics |
| Rok vydání: | 2015 |
| Předmět: |
Myelinated nerve fiber
Ubiquitin-Protein Ligases Biology Nerve Fibers Myelinated Biochemistry Mice Myelin Peripheral Nervous System medicine Animals Humans Remyelination Molecular Biology Myelin Sheath Mice Knockout Myelin protein zero Gene Expression Regulation Developmental Nuclear Proteins Peripheral Nervous System Diseases Molecular Bases of Disease Cell Biology medicine.disease Protein Inhibitors of Activated STAT Sciatic Nerve Nerve Regeneration Protein Structure Tertiary Myelin basic protein Cell biology Peripheral neuropathy medicine.anatomical_structure nervous system Peripheral nervous system Immunology biology.protein Additions and Corrections Schwann Cells Sciatic nerve |
| Zdroj: | Journal of Biological Chemistry, 290(2), 727-743. American Society for Biochemistry and Molecular Biology Inc. |
| ISSN: | 0021-9258 |
| Popis: | The transcription factor Miz1 (Myc-interacting zinc finger 1) is a known regulator of the cell cycle but also has cell cycle-independent functions. Here we analyzed the role of Miz1 in the peripheral nervous system, using an early embryonic conditional knock-out model in which the Miz1 POZ domain is ablated in Schwann cells. Although the development of myelinated nerve fibers was not impaired, Miz1 Delta POZ mice acquired behavioral signs of a peripheral neuropathy at the age of 3 months. At this time, ultrastructural analysis of the sciatic nerve showed de-and dysmyelination of fibers, with massive outfoldings and a focal infiltration of macrophages. Although the expression of genes encoding structural myelin proteins, such as periaxin, myelin basic protein, and myelin protein zero, was decreased, genes associated with a negative regulation of myelination, including c-Jun, Sox2, and Id2, were up-regulated in Miz1 Delta POZ mice compared with controls. In animals older than 4 months, the motor disabilities vanished, and the ultrastructure of the sciatic nerve exhibited numerous tomacula and remyelinated fibers, as indicated by thinner myelin. No second acute attack was observed up to the age of 1 year. Thus, the deletion of the Miz1 POZ domain in Schwann cells induces an acute neuropathy with a subsequent regeneration in which there is ongoing balancing between de-and remyelination. Miz1 Delta POZ mice are impaired in the maintenance of myelinated fibers and are a promising model for studying remyelination in adult peripheral nerves. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|