Roles of the synaptic molecules Hevin and SPARC in mouse neuromuscular junction development and repair
| Autor: | Thomas Taetzsch, Gregorio Valdez, W. Christopher Risher, MacKenzie Miko, Shreyaska Dahal, Vanessa L. Brayman |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mice 129 Strain Neuromuscular Junction Mice Transgenic Biology Neuromuscular junction Article Extracellular matrix Synapse Myoblasts 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Osteonectin Gene knockout Cells Cultured Acetylcholine receptor Mice Knockout Extracellular Matrix Proteins General Neuroscience Calcium-Binding Proteins Skeletal muscle Nerve injury Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Synapses medicine.symptom 030217 neurology & neurosurgery Reinnervation |
| Zdroj: | Neurosci Lett |
| ISSN: | 1872-7972 |
| Popis: | Hevin and secreted protein acidic and rich in cysteine (SPARC) are highly homologous matricellular proteins that function in concert to guide the formation of brain synapses. Here, we investigated the role of these glycoproteins in neuromuscular junction (NMJ) maturation, stability, and repair following injury. Hevin and SPARC mRNA levels in developing (postnatal day 9), adult (postnatal days 90 and 120), and injured (fibular nerve crush) skeletal muscles were assessed with qPCR. Muscle fiber size was analyzed in developing (P9) mice lacking SPARC, Hevin, and both SPARC and Hevin. NMJ morphology was assessed in developing (P9), adult (P90) and injured (fibular nerve crush) mice lacking SPARC, Hevin, and both SPARC and Hevin skeletal muscle. Hevin and SPARC are expressed in skeletal muscles and are upregulated following nerve injury. Hevin(−/−) mice exhibited delayed NMJ and muscle fiber development but displayed normal NMJ morphology in adulthood and accelerated NMJ reinnervation following nerve injury. Mice lacking SPARC displayed normal NMJ and muscle fiber development but exhibited smaller NMJs with fewer acetylcholine receptor islands in adulthood. Further, SPARC deletion did not result in overt changes in NMJ reformation following nerve injury. The combined deletion of Hevin and SPARC had little effect on NMJ phenotypes observed in single knockouts, however deletion of SPARC in combination with Hevin reversed deficiencies in muscle fiber maturation observed in Hevin(−/−) muscle. These results identify SPARC and Hevin as extracellular matrix proteins with roles in NMJ development and repair. |
| Databáze: | OpenAIRE |
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