International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Dr Deborah Cabin
49 Convent Dr.
Building 49, Room 4B67
Bethesda 20892

Co-Authors:  1)Murphy D, 2)Gottschalk W, 2)Lu B, 3)Nussbaum R
Institutions:   1)NINDS/NIH, 2)NICHD/NIH, 3)NHGRI/NIH

Depletion of a subset of synaptic vesicles in mice lacking a-synuclein

Mutations in the a-synuclein gene (SNCA) are responsible for a subset of familial forms of Parkinson's disease.  The function of the SNCA protein is unknown, but it is the major component of Lewy bodies, the neuronal inclusions that are diagnostic for Parkinsons disease.  Mice homozygous for a targeted deletion in Snca produce no a-syncuclein detectable on Western blots, and are viable, healthy, and appear to have normal life spans.  As the protein is presynaptic, electron microscopy was used to examine synaptic structure in both cultured hippocampal neurons and in hippocampal sections.  Mutant animals had significantly fewer synaptic vesicles in the vesicle cluster proximal to the docked vesicle pool.  Two electrophysiological paradigms were used to determine if this difference is reflected in synaptic function.  No difference was seen between mutant and wild type mice in response to a train of high frequency stimuli sufficient to exhaust docked synaptic vesicles.  A prolonged course of low frequency stimuli in which the reserve pool of synaptic vesicles is believed to be utilized suggests that this pool is depleted more quickly in the mutant than in normal mice.  Snca thus seems to play a role in the production or maintenance of a subset of synaptic vesicles.  cDNA subtraction experiments are now underway to determine if these phenotypes are associated with changes in gene expression in the mutant mice.

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