Mouse models of Machado-Joseph disease and other polyglutamine spinocerebellar ataxias.
Machado-Joseph disease (MJD), also called spinocerebellar ataxia type 3, is caused by mutant ataxin-3 with a polyglutamine expansion. Although there is no treatment available at present to cure or delay the onset of MJD, mouse models have been generated to facilitate the development of a therapy. In this review, the published reports on mouse models of MJD and other polyglutamine spinocerebellar ataxias are compared. Based on these studies, the following approaches will be discussed as candidate treatments for MJD: 1) interfering with the formation of the mutant ataxin-3 cleavage fragment and possibly aggregate or inclusions, 2) reducing the disease protein nuclear localization, and 3) decreasing mutant ataxin-3 expression in neurons.
Colomer Gould
Veronica F
VF
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. vcolomer@jhu.edu
D000818:Animals; D000067699:Ataxin-3; D001923:Brain Chemistry / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D017827:Machado-Joseph Disease / Q000235:genetics*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins; D010455:Peptides / Q000235:genetics* / Q000502:physiology*; D012097:Repressor Proteins; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D014157:Transcription Factors
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D012097:Repressor Proteins; D014157:Transcription Factors; C097188:polyglutamine; C092341:ATXN3 protein, human; D000067699:Ataxin-3; C511594:Atxn3 protein, mouse