Résumé :
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Progressive motor neuronopathy (pmn) is a particularly aggressive form of motor neuron disease characterized by early loss of neuromuscular synapses and axonal dying back (Schmalbruch et al., 1991). We previously identified the genetic defect of pmn mice as a missense mutation in TBCE, one of five tubulin chaperones required for tubulin folding and dimerisation (Martin et al. 2002). We further demonstrated that TBCE is a Golgi-associated protein that controls axonal tubulin routing and microtubule maintenance (Schäfer et al. 2007). To monitor the morphological and molecular correlates of progressive motor neuronopathy we now crossbred pmn mice with transgenic thy1-YFP-reporter mice (Feng et al. 2000) and labelled whole mount nerve-muscle preparations from endstage mice for VAChT (vesicular acetylcholine transporter), synaptic vesicle proteins and acetylcholine receptors. Axon degeneration was attested by calibre irregularities of YFP-positive axons, axonal spheroids and loss of axonal continuity. Degeneration of neuromuscular synapses was evidenced by reduced VaChT levels in presynaptic terminals and by altered distribution of postsynaptic acetylcholine receptor clusters. These degenerative changes were most pronounced in the diaphragm and more moderate in the gluteus and superficial abdominal muscles. Thy1 YFP mice thus represent a powerful tool to monitor temporal progression and spatial distribution of axon and synapse degeneration in mouse motor neuron disease.
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