Human Molecular Genetics, Vol 6, 1633-1637, Copyright © 1997 by Oxford University Press
GP Bates, L Mangiarini, A Mahal and SW Davies
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.
REVIEWS
Transgenic models of Huntington's disease
Medical and Molecular Genetics, UMDS, Guy's Hospital, London, UK. g.bates@umds.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Seo, W. Kim, and O. Isacson Compensatory changes in the ubiquitin-proteasome system, brain-derived neurotrophic factor and mitochondrial complex II/III in YAC72 and R6/2 transgenic mice partially model Huntington's disease patients Hum. Mol. Genet., October 15, 2008; 17(20): 3144 - 3153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gonitel, H. Moffitt, K. Sathasivam, B. Woodman, P. J. Detloff, R. L. M. Faull, and G. P. Bates DNA instability in postmitotic neurons PNAS, March 4, 2008; 105(9): 3467 - 3472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Albertelli, A. Scheller, M. Brogley, and D. M. Robins Replacing the Mouse Androgen Receptor with Human Alleles Demonstrates Glutamine Tract Length-Dependent Effects on Physiology and Tumorigenesis in Mice Mol. Endocrinol., June 1, 2006; 20(6): 1248 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, D. D. Mosser, and J. Bag Induction of HSP70 expression and recruitment of HSC70 and HSP70 in the nucleus reduce aggregation of a polyalanine expansion mutant of PABPN1 in HeLa cells Hum. Mol. Genet., December 1, 2005; 14(23): 3673 - 3684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Rub, D. Del Turco, K. Del Tredici, R. A. I. de Vos, E. R. Brunt, G. Reifenberger, C. Seifried, C. Schultz, G. Auburger, and H. Braak Thalamic involvement in a spinocerebellar ataxia type 2 (SCA2) and a spinocerebellar ataxia type 3 (SCA3) patient, and its clinical relevance Brain, October 1, 2003; 126(10): 2257 - 2272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Dorsman, B. Pepers, D. Langenberg, H. Kerkdijk, M. Ijszenga, J. T. den Dunnen, R.A.C. Roos, and G.-J. B. van Ommen Strong aggregation and increased toxicity of polyleucine over polyglutamine stretches in mammalian cells Hum. Mol. Genet., June 15, 2002; 11(13): 1487 - 1496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Panigrahi, J. D. Cleary, and C. E. Pearson In Vitro (CTG){middle dot}(CAG) Expansions and Deletions by Human Cell Extracts J. Biol. Chem., April 12, 2002; 277(16): 13926 - 13934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Popoli, A. Pintor, M. R. Domenici, C. Frank, M. T. Tebano, A. Pezzola, L. Scarchilli, D. Quarta, R. Reggio, F. Malchiodi-Albedi, et al. Blockade of Striatal Adenosine A2A Receptor Reduces, through a Presynaptic Mechanism, Quinolinic Acid-Induced Excitotoxicity: Possible Relevance to Neuroprotective Interventions in Neurodegenerative Diseases of the Striatum J. Neurosci., March 1, 2002; 22(5): 1967 - 1975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Peel, R. V. Rao, B. A. Cottrell, M. R. Hayden, L. M. Ellerby, and D. E. Bredesen Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue Hum. Mol. Genet., July 1, 2001; 10(15): 1531 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dodd, P. M. Curtis, L. C. Williams, and D. R. Love Zebrafish: bridging the gap between development and disease Hum. Mol. Genet., October 1, 2000; 9(16): 2443 - 2449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, S.-H. Li, A. L. Cheng, L. Mangiarini, G. P. Bates, and X.-J. Li Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice Hum. Mol. Genet., July 1, 1999; 8(7): 1227 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Smith, L. Whitesell, and E. Katsanis Molecular Chaperones: Biology and Prospects for Pharmacological Intervention Pharmacol. Rev., December 1, 1998; 50(4): 493 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Rowland Molecular Basis of Genetic Heterogeneity: Role of the Clinical Neurologist J Child Neurol, March 1, 1998; 13(3): 122 - 132. [Abstract] [PDF]
|
|