Journal ArticleDOI
Choosing an animal model for the study of Huntington's disease
TLDR
This Review provides an overview of the currently available animal models of HD in the context of the clinical features of the disease and highlights their strengths and limitations for modelling specific symptoms of the Disease.Abstract:
Since the identification of the causative gene in Huntington's disease (HD), a number of animal models of this disorder have been developed. A frequently asked question is: which of these models most closely recapitulates the human disease? In this Review, we provide an overview of the currently available animal models of HD in the context of the clinical features of the disease. In doing so, we highlight their strengths and limitations for modelling specific symptoms of the disease. This should highlight the animal model that is best suited to address a particular question of interest and, ultimately, to expedite the discovery of treatments that will prevent or slow the progression of HD.read more
Citations
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Journal ArticleDOI
Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice
Xiaoping Tong,Yan Ao,Guido C. Faas,Sinifunanya E. Nwaobi,Ji Xu,Martin D. Haustein,Mark Anderson,Istvan Mody,Michelle L. Olsen,Michael V. Sofroniew,Baljit S. Khakh +10 more
TL;DR: It is found that symptom onset in R6/2 and Q175 HD mouse models was not associated with classical astrogliosis, but was associated with decreased Kir4.1 K+ channel functional expression, leading to elevated in vivo striatal extracellular K+, which increased MSN excitability in vitro.
Journal ArticleDOI
Extrasynaptic NMDA Receptor Involvement in Central Nervous System Disorders
TL;DR: Evidence both supporting and refuting the localization hypothesis of NMDAR function is reviewed and the role of N MDAR localization in disorders of the nervous system is discussed, particularly in Alzheimer disease and Huntington disease.
Journal ArticleDOI
Integrated genomics and proteomics define huntingtin CAG length–dependent networks in mice
Peter Langfelder,Jeffrey P. Cantle,Jeffrey P. Cantle,Doxa Chatzopoulou,Nan Wang,Nan Wang,Fuying Gao,Fuying Gao,Ismael Al-Ramahi,Ismael Al-Ramahi,Xiao-Hong Lu,Xiao-Hong Lu,Eliana Marisa Ramos,Eliana Marisa Ramos,Karla El-Zein,Karla El-Zein,Yining Zhao,Sandeep Deverasetty,Andreas Tebbe,Christoph Schaab,Daniel J. Lavery,David Howland,Seung Kwak,Juan Botas,Juan Botas,Jeffrey S. Aaronson,Jim Rosinski,Giovanni Coppola,Steve Horvath,X. William Yang,X. William Yang +30 more
TL;DR: Proteomics was used to confirm 790 genes and 5 striatal modules with CAG length–dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.
Journal ArticleDOI
'The clocks that time us'--circadian rhythms in neurodegenerative disorders.
TL;DR: The role of the circadian system in the regulation of the sleep–wake cycle is discussed, and the implications of disrupted circadian timekeeping in neurodegenerative diseases are outlined.
Journal ArticleDOI
Mutant Huntingtin Disrupts the Nuclear Pore Complex
Jonathan C. Grima,J. Gavin Daigle,Nicolas Arbez,Kathleen C. Cunningham,Ke Zhang,Joseph Ochaba,Charlene Geater,Eva L. Morozko,Jennifer Stocksdale,Jenna C. Glatzer,Jacqueline T. Pham,Ishrat Ahmed,Qi Peng,Harsh Wadhwa,Olga Pletnikova,Juan C. Troncoso,Wenzhen Duan,Solomon H. Snyder,Laura P.W. Ranum,Leslie M. Thompson,Thomas E. Lloyd,Christopher A. Ross,Jeffrey D. Rothstein +22 more
TL;DR: This work evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions, and revealed severe mislocalization and aggregation of NUPs and defective nucleocy toplasmi transport.
References
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Journal ArticleDOI
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Andrea H. Brand,Norbert Perrimon +1 more
TL;DR: The GAL4 system, a system for targeted gene expression that allows the selective activation of any cloned gene in a wide variety of tissue- and cell-specific patterns, has been designed and used to expand the domain of embryonic expression of the homeobox protein even-skipped.
Journal ArticleDOI
Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice
Laura Mangiarini,Kirupa Sathasivam,Mary J. Seller,Barbara A. Cozens,Alex Harper,Colin Hetherington,Martin Lawton,Yvon Trottier,Hans Lehrach,Stephen W. Davies,Gillian P. Bates +10 more
TL;DR: Mice have been generated that are transgenic for the 5' end of the human HD gene carrying CAG/polyglutamine repeat expansion that exhibits many of the features of HD, including choreiform-like movements, involuntary stereotypic movements, tremor, and epileptic seizures.
Journal ArticleDOI
Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain
Marian DiFiglia,Ellen Sapp,Kathryn Chase,Stephen W. Davies,Gillian P. Bates,J. P. Vonsattel,Neil Aronin +6 more
TL;DR: An NH2-terminal fragment of mutant huntingtin was localized to neuronal intranuclear inclusions and dystrophic neurites in the HD cortex and striatum, and polyglutamine length influenced the extent of huntingtin accumulation in these structures.
Journal ArticleDOI
Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the hd mutation
Stephen W. Davies,Mark Turmaine,Barbara A. Cozens,Marian DiFiglia,Alan H. Sharp,Christopher A. Ross,Eberhard Scherzinger,Erich E. Wanker,Laura Mangiarini,Gillian P. Bates +9 more
TL;DR: In this paper, the authors observed that mice transgenic for exon 1 of the human HD gene carrying (CAG)115 to 157 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype.
Journal ArticleDOI
Huntington's disease.
TL;DR: Effective intervention by clinicians is possible in terms of providing patients and families with accurate information about the disease, counseling them about availability of genetic testing at specialized centers, and in giving them sound advice regarding work, driving, relationships, finances, research participation, and support groups.
Related Papers (5)
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
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A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
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