Progressive depletion of complexin II in a transgenic mouse model of Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disord er characterized by motor, emotional and cognitive dysfunction. There is no treatment or cure for this disease, and after the onset of symptoms, usual ly in the fourth decade of life, there is an inexorable decline to death. i n many patients there is a complex deterioration of function before the ons et of neuronal loss and, at least in mouse models, abnormalities in neurotr ansmission represent early events in the development of the disease. Here w e describe the specific and progressive loss of complexin II from the brain s of mice carrying the HD mutation (R6/2 line), and the later appearance of this protein in a subpopulation of neuronal intranuclear inclusions. Altho ugh the precise role of complexin ii is still unclear, it is known to bind to the SNARE complex, and is therefore likely to be involved in the control of exocytosis. Our results suggest that changes in neurotransmitter releas e might contribute to the neuronal dysfunction seen in these mice.