Characterization of a Drosophila model of Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurological disorder caused by a polyglutamine (polyQ) repeat expansion in the huntingtin (Htt) protein. The disease is characterized by neurodegeneration and formation of neuronal intracellular inclusions primarily in the striatum and cortex, leading to personality changes, motor impairment, and dementia. To date, the molecular mechanisms that underlie the neurodegenerative process remain to be defined. Development of transgenic Drosophila HD models may facilitate dissection of molecular and cellular pathways that lead to disease pathology and suggest potential strategies for treatment. To explore mutant Htt-mediated mechanisms of neuronal dysfunction, we generated transgenic Drosophila that express the first 548 amino acids of the human Htt gene with either a pathogenic polyglutamine tract of 128 repeats (Htt-Q128) or a nonpathogenic tract of 0 repeats (Htt-QO). Characterization of these transgenic lines indicates formation of cytoplasmic and neuritic Htt aggregates in our Drosophila HD model that sequester other non-nuclear polyQ-containing proteins and block axonal transport.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Lee, Wyan-Ching Mimi

Advisor dc:contributor.advisor

• J. Troy Littleton.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34571
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34571

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34571