Huntington's disease (HD) is an inherited, neurodegenerative disorder
caused by expansion of a CAG repeat in the IT15 gene, leading to an ex
panded 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 conducte
d quantitative Western blot analyses of HD patients and controls. Expr
ession of the IT15 protein is essentially equal in control and HD fron
tal 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 e
xpression of the two alleles of the IT15 protein we used Western blots
of 4% polyacrylamide gels, Both alleles of the IT15 protein were expr
essed at similar levels in HD lymphoblastoid cell lines and HD post-mo
rtem hippocampus and cerebellum (regions relatively spared in HD), ind
icating that even very long CAG repeats can be translated into polyglu
tamine, In contrast, in cerebral cortex and caudate (regions severely
affected in HD), in the longer expanded repeat cases the expanded alle
le of the IT15 protein was present at a significantly lower level (com
pared with the normal length allele), often with a smear of more slowl
y migrating reactivity above it, These data suggest the possibility of
altered structure, abnormal processing or abnormality of protein-prot
ein interactions involving the IT15 protein with the expanded glutamin
e repeat.