SHANK3 deficiency leads to myelin defects in the central and peripheral nervous system
| Autor: | Mariagiovanna Malara, Anne-Kathrin Lutz, Berra Incearap, Helen Friedericke Bauer, Silvia Cursano, Katrin Volbracht, Joanna Janina Lerner, Rakshita Pandey, Jan Philipp Delling, Valentin Ioannidis, Andrea Pérez Arévalo, Jaime Eugenin von Bernhardi, Michael Schön, Jürgen Bockmann, Leda Dimou, Tobias M. Boeckers |
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| Přispěvatelé: | European Union (EU), Horizon 2020 |
| Jazyk: | angličtina |
| Předmět: |
genetics [Chromosome Disorders]
Autism Spectrum Disorder Chromosomes Human Pair 22 Chromosome Disorders Nerve Tissue Proteins Autismus ASD Mice Cellular and Molecular Neuroscience ddc:150 pathology [Myelin Sheath] metabolism [Peripheral Nervous System] Peripheral Nervous System Shank3 protein mouse Animals Humans ddc:610 SHANK3 Molecular Biology Myelin Sheath genetics [Nerve Tissue Proteins] Mice Knockout Pharmacology hiPSCs DDC 150 / Psychology Microfilament Proteins SHANK3 protein human Cell Biology Autism spectrum disorders Myelin metabolism [Chromosome Disorders] Molecular Medicine genetics [Autism Spectrum Disorder] Chromosome Deletion genetics [Microfilament Proteins] |
| Zdroj: | Cellular and molecular life sciences 79(7), 371 (2022). doi:10.1007/s00018-022-04400-4 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-022-04400-4 |
| Popis: | Mutations or deletions of the SHANK3 gene are causative for Phelan–McDermid syndrome (PMDS), a syndromic form of autism spectrum disorders (ASDs). We analyzed Shank3Δ11(−/−) mice and organoids from PMDS individuals to study effects on myelin. SHANK3 was found to be expressed in oligodendrocytes and Schwann cells, and MRI analysis of Shank3Δ11(−/−) mice revealed a reduced volume of the corpus callosum as seen in PMDS patients. Myelin proteins including myelin basic protein showed significant temporal and regional differences with lower levels in the CNS but increased amounts in the PNS of Shank3Δ11(−/−) animals. Node, as well as paranode, lengths were increased and ultrastructural analysis revealed region-specific alterations of the myelin sheaths. In PMDS hiPSC-derived cerebral organoids we observed an altered number and delayed maturation of myelinating cells. These findings provide evidence that, in addition to a synaptic deregulation, impairment of myelin might profoundly contribute to the clinical manifestation of SHANK3 deficiency. publishedVersion |
| Databáze: | OpenAIRE |
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