title: Mouse models of Huntington disease: variations on a theme.
abstract: An accepted prerequisite for clinical trials of a compound in humans is the successful alleviation of the disease in animal models. For some diseases, however, successful translation of drug effects from mouse models to the bedside has been limited. One question is whether the current models accurately reproduce the human disease. Here, we examine the mouse models that are available for therapeutic testing in Huntington disease (HD), a late-onset neurodegenerative disorder for which there is no effective treatment. The current mouse models show different degrees of similarity to the human condition. Significant phenotypic differences are seen in mouse models that express either truncated or full-length human, or full-length mouse, mutant huntingtin (mHTT). These differences in phenotypic expression may be attributable to the influences of protein context, mouse strain and a difference in regulatory sequences between the mouse Htt and human HTT genes.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, Canada.
authors.forename: Dagmar E
authors.initials: DE
authors.lastname: Ehrnhoefer
authors.forename: Stefanie L
authors.initials: SL
authors.lastname: Butland
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Pouladi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D000818:Animals; D001665:Binding Sites; D004195:Disease Models, Animal; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors