Korean J Pediatr.  2005 Apr;48(4):425-432.

Expression of Expanded Polyglutamine Disease Proteins in Drosophila (Drosophila Polyglutamine Disease Models)

• Shin SM
• Paik KH
• Jin DK

Abstract

PURPOSE
Polyglutamine diseases are a group of diseases caused by the expansion of a polyglutamine tract in the protein. The present study was performed to verify if polyglutamine disease transgenic Drosophila models show similar dysfunctions as are seen in human patients.
METHODS
Polyglutamine disease transgenic Drosophila were tested for their climbing ability. And using genetic methods, the effects of anti-apoptotic gene bcl-2 and chemical chaperones on neurodegeneration were observed. Also, spinocerebellar ataxia 2 (SCA2) transgenic Drosophila lines were generated for future studies.
RESULTS
Expanded forms of spinocerebellar ataxia 3 (SCA3) transgenic protein causes characteristic locomotor dysfunction when expressed in the nervous system of Drosophila but the anti-apoptotic gene bcl-2 shows no evidence of ameliorating the deleterious effect of the expanded protein. However, Glycerol, a chemical chaperone, seemed to reduce the toxicity, at least in the eyes of the transgenic flies. The level SCA2 expression is too weak in the transgenic SCA2 Drosophila for evaluation.
CONCLUSION
SCA3 transgenic Drosophila show ataxic behavior as observed in human patients. Chemical chaperones such as glycerol may prove beneficial in this class of genetic disease, which has no current method of cure.

Keyword

Polyglutamine; Machdo-Joseph disease (MJD); Spinocerebellar ataxia 3 (SCA3); Drosophila; Behavioral dysfunction; bcl-2; Spinocerebellar ataxia 2 (SCA2); Chaperones

MeSH Terms

Diptera
Drosophila*
Glycerol
Humans
Machado-Joseph Disease
Nervous System
Spinocerebellar Ataxias
Glycerol