Progressive depletion of complexin II in a transgenic mouse model of Huntington's disease.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, emotional and cognitive dysfunction. There is no treatment or cure for this disease, and after the onset of symptoms, usually in the fourth decade of life, there is an inexorable decline to death. In many patients there is a complex deterioration of function before the onset of neuronal loss and, at least in mouse models, abnormalities in neurotransmission represent early events in the development of the disease. Here we describe the specific and progressive loss of complexin II from the brains of mice carrying the HD mutation (R6/2 line), and the later appearance of this protein in a subpopulation of neuronal intranuclear inclusions. Although 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 release might contribute to the neuronal dysfunction seen in these mice.
Morton
A J
AJ
Department of Pharmacology, University of Cambridge, Cambridge, UK. ajm41@cam.ac.uk
Edwardson
J M
JM
D033942:Adaptor Proteins, Vesicular Transport; D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D018450:Disease Progression; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D002479:Inclusion Bodies / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000378:metabolism*; D009928:Organ Specificity; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; C095993:complexin II