Differential distribution of the normal and mutated forms of huntingtin in the human brain.
Ann Neurol.. 1997-11-01; 42(5): 712-719
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1. Ann Neurol. 1997 Nov;42(5):712-9.
Differential distribution of the normal and mutated forms of huntingtin in the
Gourfinkel-An I(1), Cancel G, Trottier Y, Devys D, Tora L, Lutz Y, Imbert G,
Saudou F, Stevanin G, Agid Y, Brice A, Mandel JL, Hirsch EC.
(1)INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Huntington’s disease is an inherited disorder caused by expansion of a CAG
trinucleotide repeat in the IT15 gene, which leads to expansion of a
polyglutamine tract within the protein called huntingtin. Despite the
characterization of the IT15 gene and the mutation involved in the disease, the
normal function of huntingtin and the effects of the mutation on its function and
on its neuronal location remain unknown. To study whether mutated huntingtin has
the same neuronal distribution and intracellular location as normal huntingtin,
we analyzed immunohistochemically both forms of this protein in the brain of 5
controls and 5 patients with Huntington’s disease. We show that the distribution
of mutated huntingtin is, like that of the normal form, heterogeneous throughout
the brain, but is not limited to vulnerable neurons in Huntington’s disease,
supporting the hypothesis that the presence of the mutated huntingtin in a neuron
is not in itself sufficient to lead to neuronal death. Moreover, whereas normal
huntingtin is detected in some neuronal perikarya, nerve fibers, and nerve
endings, the mutated form is observed in some neuronal perikarya and proximal
nerve processes but is not detectable in nerve endings. Our results suggest that
the expression or processing of the mutated huntingtin in perikarya and nerve
endings differs quantitatively or qualitatively from the expression of the normal
form in the same neuronal compartments.
PMID: 9392570 [Indexed for MEDLINE]