Lessons from animal models of Huntington's disease.
Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HD gene. The expanded repeats are translated into an abnormally long polyglutamine tract close to the N-terminus of the HD gene product, huntingtin. Studies in mouse models and human suggest that the mutation is associated with a deleterious gain of function. There is now a wide range of mouse models for HD, providing important insights into processes associated with disease pathogenesis. These models have been complemented by studies in Drosophila and Caenorhabditis elegans that have allowed the identification of possible modifier loci through suppressor screens.
Rubinsztein
David C
DC
Dept of Medical Genetics, Cambridge Institute of Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK. dcr1000@cus.cam.ac.uk
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D002479:Inclusion Bodies / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000473:pathology; D009687:Nuclear Proteins / Q000502:physiology; D020080:Tandem Repeat Sequences; D025801:Ubiquitin / Q000737:chemistry / Q000502:physiology
C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D025801:Ubiquitin