Regional and progressive changes in brain expression of complexin II in a mouse transgenic for the Huntington's disease mutation.
Changes in mRNA expression of soluble NSF-attachment protein receptors (SNAREs) and SNARE-associated proteins have been shown to occur in a number of disorders such as schizophrenia, Alzheimer's disease and Parkinson's disease. We have shown previously that there is a decrease in protein levels of the SNARE-associated protein, complexin II (CPLXII) in Huntington's disease brain and in the R6/2 mouse model of Huntington's disease. In the current study, we used quantitative in situ hybridisation to examine mRNA expression of SNAREs (25 kDa synaptosome-associated protein (SNAP-25), syntaxin-1A and synaptobrevin-2) and SNARE-associated proteins (alpha-SNAP, CPLXI and CPLXII) in brain of R6/2 mice and their wild type littermates between 3 and 15 weeks of age. We found an early and progressive decrease of CPLXII expression in R6/2 mice brains. In contrast, no changes in SNARE expression were seen in R6/2 brains compared with wild type brain. Further, while decreased expression of alpha-SNAP and CPLXI was seen, this was not until 15 weeks of age and even then the changes were small. We suggest that downregulation of expression of mRNA encoding SNARE-associated proteins, first CPLXII and later CPLXI and alpha-SNAP, contributes to the progressive neuropathology of the R6/2 mouse model of Huntington's disease.
Freeman
Whitney
W
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Morton
A Jennifer
AJ
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005089:Exocytosis / Q000235:genetics; D005260:Female; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017729:Presynaptic Terminals / Q000378:metabolism*; D050683:R-SNARE Proteins; D012333:RNA, Messenger / Q000378:metabolism; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D000954:Antigens, Surface; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D012333:RNA, Messenger; D050600:SNARE Proteins; C494209:Snap25 protein, mouse; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; C494214:Stx1a protein, mouse; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; C095992:complexin I; C095993:complexin II