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Title: The effects of synuclein null mutations on murine physiology and development
Author: Robertson, Darren
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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I studied the effects of a targeted inactivation of the γ-synuclein gene on murine physiology and development, later extending these studies to include α-synuclein and α/γ-synuclein null mutant mice which I produced. All these animals are viable and fertile with no gross physiological of morphological abnormalities. A quantitative evaluation of neuronal populations within the midbrain showed a reduction in the number of depamergic neurons in the SNpc region but not in ventral tegmental area (VTA) of adult γ-synuclein null mutant mice. Similar reductions were revealed in α-synuclein and double α/γ-synuclein null mutant animals. However, in none of these mutants did this lead to significant changes in levels of striatal dopamine or dopamine metabolite levels or motor function. No similar changes were observed in peripheral sensory ganglia. In all three studied types of null mutants, dopaminergic neurons of SNpc were resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. We propose that both synucleins are important for effective survival of SNpc neurons during a critical period of development and that, in the absence of these proteins, permanent activation of compensatory mechanisms allow many neurons to survive and become resistant to certain toxic insults. We have shown that the absence of α, γ or α and γ-synuclein does not trigger any serious development or functional abnormalities. If the synuclein family are important for the correct development of the SNpc then compensatory mechanisms exist to limit the effect of their absence, not giving rise to any visible deleterious phenotype.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available