55 Neuroepithelial boundaries act as barriers to morphogenetic effects

The long-term contribution of balanced cholincrgic neurotransmission toward neuromuscular properties was studied in transgcnic mice b) expressing human acctylcholincsterasc (hAChE) in motoneurons, but not muscle. Spinal cord Cholinergic axodcndritic synapses in transgcnic mice wverc morphologically normal despite 7-fold higher AChE activity staining as compared with control synapses In contrast, although muscle extracts included only ca. 6%) of hAChE from motoneuron origin, transgcnic neuromuscular junctions were 60% larger than control ones and displayed either exaggerated or degenerated post-synaptic folds Neuromuscular impairment uas evident in grip tests at the age of 1 weeks, worsened with age and was accompanied by progressive amyotrophy and abnormal electromyogmphic potentials, rcflccting cnlargcd motor units and junctional dysfunction. The vulnerability of vertebrate neuromuscular .junctions to alterations in cholinergic ncurotransmission, highlights the morphogenic role of AChE Human AChE-expressing mice can hence be used for dissecting tllC molecular mechanisms underlying neuromuscular proprrties. FUNCTIONAL STUDIES OF THE SYNAPTIC VESICLE PROTEINS