Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons
- PMID: 9768849
- DOI: 10.1016/s0896-6273(00)80573-5
Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons
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. Amino-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.
Similar articles
-
Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease.Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3224-9. doi: 10.1073/pnas.0400243101. Epub 2004 Feb 20. Proc Natl Acad Sci U S A. 2004. PMID: 14978262 Free PMC article.
-
Amyloid formation by mutant huntingtin: threshold, progressivity and recruitment of normal polyglutamine proteins.Somat Cell Mol Genet. 1998 Jul;24(4):217-33. doi: 10.1023/b:scam.0000007124.19463.e5. Somat Cell Mol Genet. 1998. PMID: 10410676
-
Selection of behaviors and segmental coordination during larval locomotion is disrupted by nuclear polyglutamine inclusions in a new Drosophila Huntington's disease-like model.J Neurogenet. 2010 Dec;24(4):194-206. doi: 10.3109/01677063.2010.514367. J Neurogenet. 2010. PMID: 21087194
-
Huntington's disease: translating a CAG repeat into a pathogenic mechanism.Curr Opin Neurobiol. 1996 Oct;6(5):638-43. doi: 10.1016/s0959-4388(96)80097-3. Curr Opin Neurobiol. 1996. PMID: 8937828 Review.
-
Lessons from animal models of Huntington's disease.Trends Genet. 2002 Apr;18(4):202-9. doi: 10.1016/s0168-9525(01)02625-7. Trends Genet. 2002. PMID: 11932021 Review.
Cited by
-
A huntingtin peptide inhibits polyQ-huntingtin associated defects.PLoS One. 2013 Jul 4;8(7):e68775. doi: 10.1371/journal.pone.0068775. Print 2013. PLoS One. 2013. PMID: 23861941 Free PMC article.
-
Huntington's disease: the past, present, and future search for disease modifiers.Yale J Biol Med. 2013 Jun 13;86(2):217-33. Print 2013 Jun. Yale J Biol Med. 2013. PMID: 23766742 Free PMC article. Review.
-
Modeling human neurodegenerative diseases in transgenic systems.Hum Genet. 2012 Apr;131(4):535-63. doi: 10.1007/s00439-011-1119-1. Epub 2011 Dec 14. Hum Genet. 2012. PMID: 22167414 Review.
-
Mutational analysis implicates the amyloid fibril as the toxic entity in Huntington's disease.Neurobiol Dis. 2018 Dec;120:126-138. doi: 10.1016/j.nbd.2018.08.019. Epub 2018 Aug 30. Neurobiol Dis. 2018. PMID: 30171891 Free PMC article.
-
Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease.Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3224-9. doi: 10.1073/pnas.0400243101. Epub 2004 Feb 20. Proc Natl Acad Sci U S A. 2004. PMID: 14978262 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
