title: Expression of expanded polyglutamine protein induces behavioral changes in Drosophila (polyglutamine-induced changes in Drosophila).
abstract: 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.
authors.affiliation: Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul 121-742, Korea.
authors.forename: Yun-Taik
authors.initials: YT
authors.lastname: Kim
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Shin
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Lee
authors.forename: Gyeong-Moon
authors.initials: GM
authors.lastname: Kim
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: 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*
chemical_list: 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