Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination.
| Autor: | Arreguin AJ; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.; Medical Scientist Training Program (MSTP), Stony Brook University, Stony Brook, NY 11794-8651, USA., Shao Z; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA., Colognato H; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Disease models & mechanisms [Dis Model Mech] 2024 Apr 01; Vol. 17 (4). Date of Electronic Publication: 2024 May 09. |
| DOI: | 10.1242/dmm.050115 |
| Abstrakt: | Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, resulting in the loss of dystrophin, a large cytosolic protein that links the cytoskeleton to extracellular matrix receptors in skeletal muscle. Aside from progressive muscle damage, many patients with DMD also have neurological deficits of unknown etiology. To investigate potential mechanisms for DMD neurological deficits, we assessed postnatal oligodendrogenesis and myelination in the Dmdmdx mouse model. In the ventricular-subventricular zone (V-SVZ) stem cell niche, we found that oligodendrocyte progenitor cell (OPC) production was deficient, with reduced OPC densities and proliferation, despite a normal stem cell niche organization. In the Dmdmdx corpus callosum, a large white matter tract adjacent to the V-SVZ, we also observed reduced OPC proliferation and fewer oligodendrocytes. Transmission electron microscopy further revealed significantly thinner myelin, an increased number of abnormal myelin structures and delayed myelin compaction, with hypomyelination persisting into adulthood. Our findings reveal alterations in oligodendrocyte development and myelination that support the hypothesis that changes in diffusion tensor imaging seen in patients with DMD reflect developmental changes in myelin architecture. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.) |
| Databáze: | MEDLINE |
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