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Title: Characterisation of axon degeneration in a model of Tau pathology
Author: Berg, N. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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In disorders known as ‘dying-back’ neuropathies, the distal nerves appear to degenerate first and this form of degeneration has many similarities to Wallerian degeneration. In the slow Wallerian degeneration (Wlds) mouse there is a 85kb tandem triplication resulting in the expression of a chimeric protein, consisting of the first 70 amino acids of Ube4B and the full sequence of the Nmnat1 protein. In the Wlds mouse Wallerian degeneration appears to be slowed approximately ten fold. The aim of the present study was to determine whether the Wlds gene has a protective effect in neurodegeneration caused by tau pathology. In order to visualise in vivo axonal degeneration and a possible protective effect of the Wlds gene, P301S tau transgenic mice were crossed with TFP-H mice expressing yellow fluorescent protein in a subset of neurons. First it was determined whether the expression of YFP is harmful to axons, and then YFP expression was used to follow the progression of axonal pathology in the P301S mouse. The results indicate that expression of the YFP protein leads to an increase in axonal swellings in some brain regions of aged mice, older than the P301S tau used in this study. YFP expression allows visualisation of abundant broken and abnormal axons in the peripheral and central nervous systems of P301S tau transgenic, but not control mice. The Wlds gene does not rescue the axonal degeneration observed in P301S tau transgenic mice. These results indicate that YFP expression can be used for investigation in young mice, but possible pathological effects can be present in aged mice. Furthermore, the apparent lack of protection of the Wlds gene on P301S axonal pathology suggests that Wallerian degeneration is not a major player in tau-related neurodegeneration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available