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Title: Cellular and molecular properties of the neuroprotective Wlds gene
Author: Wishart, Thomas Malcolm
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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The main objectives of my research were: 1. To develop a rapid and effective method for determining the copy number of Wlds alleles in mutant and transgenic Wlds mouse lines; 2. To map the regional distribution and sub cellular localisation of the Wlds chimeric protein product within the nervous system; 3. To test the hypothesis that the expression of the constituent components of the Wlds chimeric gene is sufficient to alter mRNA levels of other genes that may themselves be downstream effectors of the Wlds neuroprotective phenotype. !. A rapid and cost effective method for genotyping was developed using quantitative real time PCR on genomic DNA from the spontaneous Wlds mutant mouse and transgenic lines. This method allows the determination of Wlds copy number (specifically a region of the N70-Ube4b portion of the Wlds gene) for genotyping and calculating insertion number in transgenic lines. 2. A highly specific antibody generated against the Wld-18 peptide confirms that the Wlds protein product is localised to neuronal nuclei. 3. Microarray analysis and quantitative real time PCR of Wlds compared with wild-type C57B16 mouse cerebellar mRNA indicated differences in expression levels for at least 11 genes outside the Wlds locus. Together, these studies suggest that the Wlds gene product functions as a bidirectional regulator of gene expression, driving up and down the transcription of several specific genes via more than one intra-nuclear signalling pathway. The summed effects of these variations in mRNA levels may be required for full expression of the Wlds neuroprotective phenotype. Identification of the genes and proteins ultimately responsible may open up new possibilities for understanding and treatment of the consequences of injury to the nervous system, whether induced by trauma or by neurodegenerative disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available