Neuron
Volume 14, Issue 5, May 1995, Pages 1065-1074
Journal home page for Neuron

Article
Widespread expression of Huntington's disease gene (IT15) protein product

https://doi.org/10.1016/0896-6273(95)90345-3Get rights and content
Under a Creative Commons license
open archive

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.

Cited by (0)

8

Present address: Departments of Psychiatry and Pathology, New England Medical Center, Boston, Massachusetts 02111.