Synaptogenesis and Myopathy Under Acetylcholinesterase Overexpression
| Autor: | Hermona Soreq, Ilana Ariel, Eran Meshorer, Ron S. Broide, Efrat Lev-Lehman, Shlomo Seidman, Tamah Evron |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Isoflurophate Transcription Genetic Neurite Transgene Molecular Sequence Data Neuromuscular Junction Synaptogenesis Mice Inbred Strains Mice Transgenic Biology Neuromuscular junction Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Tongue Internal medicine medicine Animals RNA Messenger Muscle Skeletal Myopathy DNA Primers Motor Neurons Base Sequence Reverse Transcriptase Polymerase Chain Reaction fungi Genes fos Genetic Variation Exons General Medicine Acetylcholinesterase Endocrinology medicine.anatomical_structure Gene Expression Regulation Oligodeoxyribonucleotides chemistry Synapses Cholinergic Cholinesterase Inhibitors medicine.symptom |
| Zdroj: | Journal of Molecular Neuroscience. 14:093-106 |
| ISSN: | 0895-8696 |
| Popis: | Environmental, congenital, and acquired immunological insults perturbing neuromuscular junction (NMJ) activity may induce a variety of debilitating neuromuscular pathologies. However, the molecular elements linking NMJ dysfunction to long-term myopathies are unknown. Here, we report dramatically elevated levels of mRNA encoding c-Fos and the "readthrough" (R) variant of acetylcholinesterase (AChE) in muscles of transgenic mice overexpressing synaptic (S) AChE in motoneurons and in control mice treated with the irreversible cholinesterase inhibitor diisopropylfluorophosphonate (DFP). Tongue muscles from DFP-treated and AChE-S transgenic mice displayed exaggerated neurite branching and disorganized, wasting fibers. Moreover, diaphragm muscles from both transgenic and DFP-treated mice exhibited NMJ proliferation. 2'-O-methyl-protected antisense oligonucleotides targeted to AChE mRNA suppressed feedback upregulation of AChE and ameliorated DFP-induced NMJ proliferation. Our findings demonstrate common transcriptional responses to cholinergic NMJ stress of diverse origin, and implicate deregulated AChE expression in excessive neurite outgrowth, uncontrolled synaptogenesis, and myopathology. |
| Databáze: | OpenAIRE |
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