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Title: Intrinsic and extrinsic influences on neuromuscular synaptic degeneration in Wlds mutant mice
Author: Fan, Li
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Mutant WldS mice show slow Wallerian degeneration after nerve injury. The aim of the present thesis was to extend knowledge and understanding of the protective effect of the WldS gene, and its protein product on neuromuscular synapses. I used homozygous WldS mice in studies that addressed three hypotheses: 1. Neuromuscular synaptic protection is more sensitive to WldS gene dose than axon protection; 2. Age-dependent loss of neuromuscular synaptic protection is related to changes in WldS protein expression levels; 3. Synaptic degeneration in WldS mice can be altered by other factors including stump length and blocking neurotransmitter release. To test the first hypothesis, rates of synaptic degeneration were measured in young (2 months old) heterozygous WldS mice crossbred with mice expressing Yellow Fluorescent Protein in motor neurones. The results suggest that synaptic degeneration in WldS mice is more sensitive to WldS gene-dose dependence than axon degeneration. The second hypothesis was addressed by comparing synaptic degeneration in young (2 months old) heterozygous and homozygous WldS mice with older (>6 months) homozygous WldS mice. Immunofluorescence measurements showed obviously reduced WldS protein levels in old homozygous WldS mice. Therefore, the loss of synaptic protection in old WldS mice probably may be explained by a gene-dose dependence. The third hypothesis was addressed by comparing synaptic degeneration following sciatic nerve section versus tibial nerve section and by local injection of Botulinum toxin. Neither the length of nerve stump nor paralysis was sufficient to prevent synaptic degeneration. The data provide evidence in support of a compartmental neurodegeneration model which proposes that the survival or death of cell bodies, motor axons and terminals of motor neurones are controlled by independent regulatory mechanisms  Motor nerve terminals are an especially vulnerable neurodegenerative compartment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available