Expression of expanded polyglutamine protein induces behavioral changes in Drosophila (polyglutamine-induced changes in Drosophila).
Spinocerebellar ataxia type-3 or Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by triplet nucleotide expansion. The expansion of the polyglutamine tract near the C terminus of the MJD1 gene product, ataxin-3, above a threshold of 40 glutamine repeats causes neuronal loss and degeneration. The expanded ataxin-3 forms aggregates, and nuclear inclusions, within neurons, possibly due to the misfolding of mutant proteins. Here we report upon the behavioral test changes related to truncated and expanded forms of MJD protein (MJDtr) in Drosophila, and show that expanded MJDtr, when expressed in the nervous system, causes characteristic locomotor dysfunction and anosmia. This phenomenon has not been previously reported in humans or in transgenic Drosophila models. In addition, the in vivo expression of the antiapoptotic gene bcl-2 showed no evidence of ameliorating the deleterious effect of MJDtr-Q78s, either in the eye or in the nervous system. The study shows that such Drosophila transgenic models express olfactory dysfunction and ataxic behavior as observed in human patients.
Kim
Yun-Taik
YT
Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul 121-742, Korea.
Shin
Sang Min
SM
Lee
Won Yong
WY
Kim
Gyeong-Moon
GM
Jin
Dong Kyu
DK
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics; D000067699:Ataxin-3; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D004330:Drosophila / Q000378:metabolism*; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism; D017827:Machado-Joseph Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009069:Movement Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D000857:Olfaction Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D019680:Trinucleotide Repeat Expansion / Q000502:physiology*
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; C097188:polyglutamine; C092341:ATXN3 protein, human; D000067699:Ataxin-3