@article{1dba6de98e2842268bcf938f81a83794,
title = "Widespread expression of Huntington's disease gene (IT15) protein product",
abstract = "Huntington's Disease (HD) is caused by expansion of a CAG repeat within a putative open reading frame of a recently identified gene, IT15. We have examined the expression of the gene's protein product using antibodies developed against the N-terminus and an internal epitope. Both antisera recognize a 350 kDa protein, the predicted size, indicating that the CAG repeat is translated into polyglutamine. The HD protein product is widely expressed, most highly in neurons in the brain. There is no enrichment in the striatum, the site of greatest pathology in HD. Within neurons, the protein is diminished in nuclei and mitochondria and is present in the soluble cytoplasmic compartment, as well as loosely associated with membranes or cytoskeleton, in cell bodies, dendrites, and axons. It is concentrated in nerve terminals, including terminals within the caudate and putamen. Thus, the normal HD gene product maybe involved in common intracellular functions, and possibly in regulation of nerve terminal function. The product of the expanded allele is expressed, consistent with a gain of function mechanism for HD at the protein level.",
author = "Sharp, {Alan H.} and Loev, {Scott J.} and Gabriele Schilling and Li, {Shi Hua} and Li, {Xiao Jiang} and Jun Bao and Wagster, {Molly V.} and Kotzuk, {Joyce A.} and Steiner, {Joseph P.} and Amy Lo and John Hedreen and Sangram Sisodia and Snyder, {Solomon H.} and Dawson, {Ted M.} and Ryugo, {David K.} and Ross, {Christopher A.}",
note = "Funding Information: All correspondence should be addressed to C. A. R. This research was supported by NINDS P01 NS16375, by funds from the Department of Psychiatry, the Department of Neuroscience, and the DeVilbis fund, by a bequest from the estate of Nora Mae Gee, and by funds from the Washington Chapter of the HDSA. T. M. D. is supported by NIH CIDA NS 01578, the International Life Science Institute, and a gift from Fujisawa Pharmaceuticals. D. K. R. is supported by NIH grants DC00232 and DC00979. We thank Tan Pongstaporn for expert assistance with electron microscopy; Pietro De Camilli and Peter McPherson for helpful discussions and the generous gift of antibodies to p145 and dynamin; Yvonne Trottier of Jean-Louis Manders laboratory for helpful discussions and for the suggestion to use 4% gels to Visualize the expanded alleles; Juan C. Troncoso, M. D., for graciously providing control human autopsy striatal tissue; Olivier Blondel for the suggestion to make soluble peptides for the Western blot control experiments; Dr. Gloria E. Hoffman for advice on the biotinyl-tyramide amplification procedure for immunohistochemistry; R. T. Tracey for assistance with photography and for printing of photomicrographs; Debbie Pollard for expert word processing; and Marshal and Susan Folstein and Paul McHugh for support and guidance.",
year = "1995",
month = may,
doi = "10.1016/0896-6273(95)90345-3",
language = "English (US)",
volume = "14",
pages = "1065--1074",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}