Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons

George R. Jackson, Iris Salecker, Xinzhong Dong, Xiang Yao, Norman Arnheim, Peter W. Faber, Marcy E. MacDonald, S. Lawrence Zipursky

Research output: Contribution to journalArticle

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Disease alleles contain a trinucleotide repeat expansion of variable length, which encodes polyglutamine tracts near the amino terminus of the HD protein, huntingtin. Polyglutamine-expanded huntingtin, but not normal huntingtin, forms nuclear inclusions. We describe a Drosophila model for HD. Amine-terminal fragments of human huntingtin containing tracts of 2, 75, and 120 glutamine residues were expressed in photoreceptor neurons in the compound eye. As in human neurons, polyglutamine-expanded huntingtin induced neuronal degeneration. The age of onset and severity of neuronal degeneration correlated with repeat length, and nuclear localization of huntingtin presaged neuronal degeneration. In contrast to other cell death paradigms in Drosophila, coexpression of the viral antiapoptotic protein, P35, did not rescue the cell death phenotype induced by polyglutamine-expanded huntingtin.

Original languageEnglish (US)
Pages (from-to)633-642
Number of pages10
JournalNeuron
Volume21
Issue number3
DOIs
StatePublished - Sep 1998

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Transgenes
Drosophila
Neurons
Huntington Disease
Cell Death
Trinucleotide Repeat Expansion
Intranuclear Inclusion Bodies
Viral Proteins
Glutamine
Age of Onset
Neurodegenerative Diseases
Amines
Alleles
Phenotype
polyglutamine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Jackson, G. R., Salecker, I., Dong, X., Yao, X., Arnheim, N., Faber, P. W., ... Zipursky, S. L. (1998). Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron, 21(3), 633-642. https://doi.org/10.1016/S0896-6273(00)80573-5

Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. / Jackson, George R.; Salecker, Iris; Dong, Xinzhong; Yao, Xiang; Arnheim, Norman; Faber, Peter W.; MacDonald, Marcy E.; Zipursky, S. Lawrence.

In: Neuron, Vol. 21, No. 3, 09.1998, p. 633-642.

Research output: Contribution to journalArticle

Jackson, GR, Salecker, I, Dong, X, Yao, X, Arnheim, N, Faber, PW, MacDonald, ME & Zipursky, SL 1998, 'Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons', Neuron, vol. 21, no. 3, pp. 633-642. https://doi.org/10.1016/S0896-6273(00)80573-5
Jackson, George R. ; Salecker, Iris ; Dong, Xinzhong ; Yao, Xiang ; Arnheim, Norman ; Faber, Peter W. ; MacDonald, Marcy E. ; Zipursky, S. Lawrence. / Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. In: Neuron. 1998 ; Vol. 21, No. 3. pp. 633-642.
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