Transgenic acetylcholinesterase induces enlargement of murine neuromuscular junctions but leaves spinal cord synapses intact.
Acetylcholinesterase (AChE) produced by spinal cord motoneurons accumulates within axo-dendritic spinal cord synapses. It is also secreted from motoneuron cell bodies, through their axons, into the region of neuromuscular junctions, where it terminates cholinergic neurotransmission. Here we show that transgenic mice expressing human AChE in their spinal cord motoneurons display primarily normal axo-dendritic spinal cord cholinergic synapses in spite of the clear excess of transgenic over host AChE within these synapses. This is in contrast to our recent observation that a modest excess of AChE drastically affects the structure and long-term functioning of neuromuscular junctions in these mice although they express human AChE in their spinal cord, but not muscle. Enlarged muscle endplates with either exaggerated or drastically shortened post-synaptic folds then lead to a progressive neuromotor decline and massive amyotrophy (Andres et al., 1997). These findings demonstrate that excess neuronal AChE may cause distinct effects on spinal cord and neuromuscular synapses and attribute the late-onset neuromotor deterioration observed in AChE transgenic mice to neuromuscular junction abnormalities.
Department of Biological Chemistry, The Hebrew University of Jerusalem, Israel.
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C
Andres
S
S
Seidman
R
R
Beeri
R
R
Timberg
H
H
Soreq
D000110:Acetylcholinesterase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D003964:Diaphragm / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic / Q000235:genetics; D008854:Microscopy, Electron; D009045:Motor Endplate / Q000502:physiology / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000502:physiology* / Q000648:ultrastructure*; D013116:Spinal Cord / Q000502:physiology* / Q000648:ultrastructure*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D000110:Acetylcholinesterase