Transgenic Models of Huntington's Disease

CAG/polyglutamine expansion has been shown to form the molecular basis of an increasing number of inherited neurodegenerative diseases. The mutation is likely to act by a dominant gain of function but the mechanism by which it leads to neuronal dysfunction and cell death is unknown. The proteins har...

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Bibliographic Details
Published in:Human molecular genetics 1997-01, Vol.6 (10), p.1633-1637
Main Authors: Bates, Gillian P., Mangiarini, Laura, Mahal, Amarbirpal, Davies, Stephen W.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Humans
Huntingtin Protein
Huntington Disease - genetics
Medical sciences
Mice
Mice, Knockout
Mice, Transgenic
Mutation
Nerve Tissue Proteins - deficiency
Nerve Tissue Proteins - genetics
Neurology
Nuclear Proteins - deficiency
Nuclear Proteins - genetics
Trinucleotide Repeats
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Description
Summary:CAG/polyglutamine expansion has been shown to form the molecular basis of an increasing number of inherited neurodegenerative diseases. The mutation is likely to act by a dominant gain of function but the mechanism by which it leads to neuronal dysfunction and cell death is unknown. The proteins harbouring these polyglutamine tracts are unrelated and without exception are widely expressed with extensively overlapping expression patterns. The factors governing the cell specific nature of the neurodegeneration have yet to be understood. Upon a certain size threshold, expanded CAG repeats become unstable on transmission and a modest degree of somatic mosaicism is apparent. Similarly, the molecular basis of the instability and its tissue specificity has yet to be unravelled. Recent reports describing the first mouse models of CAG/polyglutamine disorders indicate that it will be possible to model both the pathogenic mechanism and the CAG repeat instability in the mouse. This has great potential and promise for uncovering the molecular basis of these diseases and developing therapeutic interventions.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/6.10.1633