Expression of the huntington's disease (IT15) protein product in HD patients

Gabrlele Schilling, Alan H. Sharp, Scott J. Loev, Molly V. Wagster, Shi Hua Li, O. Colin Stine, Christopher A. Ross

Research output: Contribution to journalArticlepeer-review


Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by expansion of a CAG repeat in the IT15 gene, leading to an expanded glutamine repeat in the HD protein. The mechanism by which the expanded repeat causes expression of the disease is not known, though there do not appear to be changes in the mRNA levels. We have conducted quantitative Western blot analyses of HD patients and controls. Expression of the IT15 protein is essentially equal in control and HD frontal cortex. In caudate from HD patients, IT15 protein is decreased in parallel with the decrease in a neuronal marker, suggesting that loss of IT15 protein is secondary to neuronal loss. In order to determine expression of the two alleles of the IT15 protein we used Western blots of 4% polyacrylamide gels. Both alleles of the IT15 protein were expressed at similar levels in HD lymphoblastoid cell lines and HD post-mortem hippocampus and cerebellum (regions relatively spared in HD), indicating that even very long CAG repeats can be translated into polyglutamine. In contrast, in cerebral cortex and caudate (regions severely affected in HD), in the longer expanded repeat cases the expanded allele of the IT15 protein was present at a significantly lower level (compared with the normal length allele), often with a smear of more slowly migrating reactivity above it. These data suggest the possibility of altered structure, abnormal processing or abnormality of protein-protein interactions involving the IT15 protein with the expanded glutamine repeat.

Original languageEnglish (US)
Pages (from-to)1365-1371
Number of pages7
JournalHuman molecular genetics
Issue number8
StatePublished - Aug 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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