Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (122)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Luthi-Carter, R.
Right arrow Articles by Olson, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luthi-Carter, R.
Right arrow Articles by Olson, J. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 17 1911-1926
© 2002 Oxford University Press

Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain

Ruth Luthi-Carter1, Sarah A. Hanson1, Andrew D. Strand2, Donald A. Bergstrom2, Wanjoo Chun2, Nikki L. Peters1, Annette M. Woods1, Edmond Y. Chan3, Charles Kooperberg2, Dimitri Krainc1, Anne B. Young1, Stephen J. Tapscott2 and James M. Olson2,*

1Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital, Charlestown, MA 02129-4404, USA, 2Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA and 3Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5H 4H4.

Received March 12, 2002; Accepted June 24, 2002

Previous analyses of gene expression in a mouse model of Huntington's disease (R6/2) indicated that an N-terminal fragment of mutant huntingtin causes downregulation of striatal signaling genes and particularly those normally induced by cAMP and retinoic acid. The present study expands the regional and temporal scope of this previous work by assessing whether similar changes occur in other brain regions affected in Huntington's disease and other polyglutamine diseases and by discerning whether gene expression changes precede the appearance of disease signs. Oligonucleotide microarrays were employed to survey the expression of ~11 000 mRNAs in the cerebral cortex, cerebellum and striatum of symptomatic R6/2 mice. The number and nature of gene expression changes were similar among these three regions, influenced as expected by regional differences in baseline gene expression. Time-course studies revealed that mRNA changes could only reliably be detected after 4 weeks of age, coincident with development of early pathologic and behavioral changes in these animals. In addition, we discovered that skeletal muscle is also a target of polyglutamine-related perturbations in gene expression, showing changes in mRNAs that are dysregulated in brain and also muscle-specific mRNAs. The complete dataset is available at www.neumetrix.info.

* To whom correspondence should be addressed at: Fred Hutchinson Cancer Research Center, D4-100, 1100 Fairview Ave N, Seattle, WA 98109, USA. Tel: +1 2066677955; Fax: +1 2066672917; Email: jolson{at}fhcrc.org


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 ReproductionHome page
D. C Wilkerson and K. D Sarge
RNA polymerase II interacts with the Hspa1b promoter in mouse epididymal spermatozoa
Reproduction, June 1, 2009; 137(6): 923 - 929.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
C. Zabel, L. Mao, B. Woodman, M. Rohe, M. A. Wacker, Y. Klare, A. Koppelstatter, G. Nebrich, O. Klein, S. Grams, et al.
A Large Number of Protein Expression Changes Occur Early in Life and Precede Phenotype Onset in a Mouse Model for Huntington Disease
Mol. Cell. Proteomics, April 1, 2009; 8(4): 720 - 734.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Phan, M. A. Hickey, P. Zhang, M.-F. Chesselet, and K. Reue
Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models
Hum. Mol. Genet., March 15, 2009; 18(6): 1006 - 1016.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
Q. Fang, A. Strand, W. Law, V. M. Faca, M. P. Fitzgibbon, N. Hamel, B. Houle, X. Liu, D. H. May, G. Poschmann, et al.
Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease
Mol. Cell. Proteomics, March 1, 2009; 8(3): 451 - 466.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Sato, M. Miura, M. Yamada, T. Yoshida, J. D. Wood, I. Yazawa, M. Masuda, T. Suzuki, R.-M. Shin, H.-J. Yau, et al.
Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice
Hum. Mol. Genet., February 15, 2009; 18(4): 723 - 736.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. Runne, E. Regulier, A. Kuhn, D. Zala, O. Gokce, V. Perrin, B. Sick, P. Aebischer, N. Deglon, and R. Luthi-Carter
Dysregulation of Gene Expression in Primary Neuron Models of Huntington's Disease Shows That Polyglutamine-Related Effects on the Striatal Transcriptome May Not Be Dependent on Brain Circuitry
J. Neurosci., September 24, 2008; 28(39): 9723 - 9731.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Giorgini, T. Moller, W. Kwan, D. Zwilling, J. L. Wacker, S. Hong, L.-C. L. Tsai, C. S. Cheah, R. Schwarcz, P. Guidetti, et al.
Histone Deacetylase Inhibition Modulates Kynurenine Pathway Activation in Yeast, Microglia, and Mice Expressing a Mutant Huntingtin Fragment
J. Biol. Chem., March 21, 2008; 283(12): 7390 - 7400.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
E. C. Stack, A. Dedeoglu, K. M. Smith, K. Cormier, J. K. Kubilus, M. Bogdanov, W. R. Matson, L. Yang, B. G. Jenkins, R. Luthi-Carter, et al.
Neuroprotective Effects of Synaptic Modulation in Huntington's Disease R6/2 Mice
J. Neurosci., November 21, 2007; 27(47): 12908 - 12915.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. D. Strand, Z. C. Baquet, A. K. Aragaki, P. Holmans, L. Yang, C. Cleren, M. F. Beal, L. Jones, C. Kooperberg, J. M. Olson, et al.
Expression Profiling of Huntington's Disease Models Suggests That Brain-Derived Neurotrophic Factor Depletion Plays a Major Role in Striatal Degeneration
J. Neurosci., October 24, 2007; 27(43): 11758 - 11768.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Runne, A. Kuhn, E. J. Wild, W. Pratyaksha, M. Kristiansen, J. D. Isaacs, E. Regulier, M. Delorenzi, S. J. Tabrizi, and R. Luthi-Carter
Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood
PNAS, September 4, 2007; 104(36): 14424 - 14429.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Kuhn, D. R. Goldstein, A. Hodges, A. D. Strand, T. Sengstag, C. Kooperberg, K. Becanovic, M. A. Pouladi, K. Sathasivam, J.-H. J. Cha, et al.
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage
Hum. Mol. Genet., August 1, 2007; 16(15): 1845 - 1861.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Zuccato, N. Belyaev, P. Conforti, L. Ooi, M. Tartari, E. Papadimou, M. MacDonald, E. Fossale, S. Zeitlin, N. Buckley, et al.
Widespread Disruption of Repressor Element-1 Silencing Transcription Factor/Neuron-Restrictive Silencer Factor Occupancy at Its Target Genes in Huntington's Disease
J. Neurosci., June 27, 2007; 27(26): 6972 - 6983.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Sadri-Vakili, B. Bouzou, C. L. Benn, M.-O. Kim, P. Chawla, R. P. Overland, K. E. Glajch, E. Xia, Z. Qiu, S. M. Hersch, et al.
Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models
Hum. Mol. Genet., June 1, 2007; 16(11): 1293 - 1306.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. C. Stack, S. J. Del Signore, R. Luthi-Carter, B. Y. Soh, D. R. Goldstein, S. Matson, S. Goodrich, A. L. Markey, K. Cormier, S. W. Hagerty, et al.
Modulation of nucleosome dynamics in Huntington's disease
Hum. Mol. Genet., May 15, 2007; 16(10): 1164 - 1175.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Zourlidou, T. Gidalevitz, M. Kristiansen, C. Landles, B. Woodman, D. J. Wells, D. S. Latchman, J. de Belleroche, S. J. Tabrizi, R. I. Morimoto, et al.
Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation
Hum. Mol. Genet., May 1, 2007; 16(9): 1078 - 1090.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. N.T. Strehlow, J. Z. Li, and R. M. Myers
Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space
Hum. Mol. Genet., February 15, 2007; 16(4): 391 - 409.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. Tagawa, S. Marubuchi, M.-L. Qi, Y. Enokido, T. Tamura, R. Inagaki, M. Murata, I. Kanazawa, E. E. Wanker, and H. Okazawa
The Induction Levels of Heat Shock Protein 70 Differentiate the Vulnerabilities to Mutant Huntingtin among Neuronal Subtypes
J. Neurosci., January 24, 2007; 27(4): 868 - 880.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. Rockabrand, N. Slepko, A. Pantalone, V. N. Nukala, A. Kazantsev, J. L. Marsh, P. G. Sullivan, J. S. Steffan, S. L. Sensi, and L. M. Thompson
The first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis
Hum. Mol. Genet., January 1, 2007; 16(1): 61 - 77.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. M. Cummings, A. J. Milnerwood, G. M. Dallerac, V. Waights, J. Y. Brown, S. C. Vatsavayai, M. C. Hirst, and K. P.S.J. Murphy
Aberrant cortical synaptic plasticity and dopaminergic dysfunction in a mouse model of huntington's disease
Hum. Mol. Genet., October 1, 2006; 15(19): 2856 - 2868.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y. Takeshita, R. Fujinaga, C. Zhao, A. Yanai, and K. Shinoda
Huntingtin-associated protein 1 (HAP1) interacts with androgen receptor (AR) and suppresses SBMA-mutant-AR-induced apoptosis
Hum. Mol. Genet., August 1, 2006; 15(15): 2298 - 2312.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. J. Milnerwood, D. M. Cummings, G. M. Dallerac, J. Y. Brown, S. C. Vatsavayai, M. C. Hirst, P. Rezaie, and K. P.S.J. Murphy
Early development of aberrant synaptic plasticity in a mouse model of Huntington's disease
Hum. Mol. Genet., May 15, 2006; 15(10): 1690 - 1703.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Hodges, A. D. Strand, A. K. Aragaki, A. Kuhn, T. Sengstag, G. Hughes, L. A. Elliston, C. Hartog, D. R. Goldstein, D. Thu, et al.
Regional and cellular gene expression changes in human Huntington's disease brain
Hum. Mol. Genet., March 15, 2006; 15(6): 965 - 977.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. L. Benn, C. Landles, H. Li, A. D. Strand, B. Woodman, K. Sathasivam, S.-H. Li, S. Ghazi-Noori, E. Hockly, S. M.N.N. Faruque, et al.
Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease
Hum. Mol. Genet., October 15, 2005; 14(20): 3065 - 3078.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Borovecki, L. Lovrecic, J. Zhou, H. Jeong, F. Then, H. D. Rosas, S. M. Hersch, P. Hogarth, B. Bouzou, R. V. Jensen, et al.
Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease
PNAS, August 2, 2005; 102(31): 11023 - 11028.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. D. Strand, A. K. Aragaki, D. Shaw, T. Bird, J. Holton, C. Turner, S. J. Tapscott, S. J. Tabrizi, A. H. Schapira, C. Kooperberg, et al.
Gene expression in Huntington's disease skeletal muscle: a potential biomarker
Hum. Mol. Genet., July 1, 2005; 14(13): 1863 - 1876.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
N. K. Mazarakis, A. Cybulska-Klosowicz, H. Grote, T. Pang, A. Van Dellen, M. Kossut, C. Blakemore, and A. J. Hannan
Deficits in Experience-Dependent Cortical Plasticity and Sensory-Discrimination Learning in Presymptomatic Huntington's Disease Mice
J. Neurosci., March 23, 2005; 25(12): 3059 - 3066.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
B. Zucker, R. Luthi-Carter, J. A. Kama, A. W. Dunah, E. A. Stern, J. H. Fox, D. G. Standaert, A. B. Young, and S. J. Augood
Transcriptional dysregulation in striatal projection- and interneurons in a mouse model of Huntington's disease: neuronal selectivity and potential neuroprotective role of HAP1
Hum. Mol. Genet., January 15, 2005; 14(2): 179 - 189.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. J. Morton, N. I. Wood, M. H. Hastings, C. Hurelbrink, R. A. Barker, and E. S. Maywood
Disintegration of the Sleep-Wake Cycle and Circadian Timing in Huntington's Disease
J. Neurosci., January 5, 2005; 25(1): 157 - 163.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
S.-H. Li and X.-J. Li
Huntington and its Role in Neuronal Degeneration
Neuroscientist, October 1, 2004; 10(5): 467 - 475.
[Abstract] [PDF]

Home page
 J. Neurosci.Home page
C. A. Colton, Q. Xu, J. R. Burke, S. Y. Bae, J. K. Wakefield, A. Nair, W. J. Strittmatter, and M. P. Vitek
Disrupted Spermine Homeostasis: A Novel Mechanism in Polyglutamine-Mediated Aggregation and Cell Death
J. Neurosci., August 11, 2004; 24(32): 7118 - 7127.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Schilling, A. V. Savonenko, A. Klevytska, J. L. Morton, S. M. Tucker, M. Poirier, A. Gale, N. Chan, V. Gonzales, H. H. Slunt, et al.
Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice
Hum. Mol. Genet., August 1, 2004; 13(15): 1599 - 1610.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Q. Ruan, M. Lesort, M. E. MacDonald, and G. V.W. Johnson
Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway
Hum. Mol. Genet., April 1, 2004; 13(7): 669 - 681.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
T. L. Spires, H. E. Grote, N. K. Varshney, P. M. Cordery, A. van Dellen, C. Blakemore, and A. J. Hannan
Environmental Enrichment Rescues Protein Deficits in a Mouse Model of Huntington's Disease, Indicating a Possible Disease Mechanism
J. Neurosci., March 3, 2004; 24(9): 2270 - 2276.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. L. Sugars, R. Brown, L. J. Cook, J. Swartz, and D. C. Rubinsztein
Decreased cAMP Response Element-mediated Transcription: AN EARLY EVENT IN EXON 1 AND FULL-LENGTH CELL MODELS OF HUNTINGTON'S DISEASE THAT CONTRIBUTES TO POLYGLUTAMINE PATHOGENESIS
J. Biol. Chem., February 6, 2004; 279(6): 4988 - 4999.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. Obrietan and K. R. Hoyt
CRE-Mediated Transcription Is Increased in Huntington's Disease Transgenic Mice
J. Neurosci., January 28, 2004; 24(4): 791 - 796.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. Ebralidze, Y. Wang, V. Petkova, K. Ebralidse, and R. P. Junghans
RNA Leaching of Transcription Factors Disrupts Transcription in Myotonic Dystrophy
Science, January 16, 2004; 303(5656): 383 - 387.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. J. Ferrante, J. K. Kubilus, J. Lee, H. Ryu, A. Beesen, B. Zucker, K. Smith, N. W. Kowall, R. R. Ratan, R. Luthi-Carter, et al.
Histone Deacetylase Inhibition by Sodium Butyrate Chemotherapy Ameliorates the Neurodegenerative Phenotype in Huntington's Disease Mice
J. Neurosci., October 15, 2003; 23(28): 9418 - 9427.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Marcora, K. Gowan, and J. E. Lee
Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2
PNAS, August 5, 2003; 100(16): 9578 - 9583.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Okuda, H. Hattori, S. Takeuchi, J. Shimizu, H. Ueda, J. J. Palvimo, I. Kanazawa, H. Kawano, M. Nakagawa, and H. Okazawa
PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype
Hum. Mol. Genet., April 1, 2003; 12(7): 711 - 725.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. Hockly, V. M. Richon, B. Woodman, D. L. Smith, X. Zhou, E. Rosa, K. Sathasivam, S. Ghazi-Noori, A. Mahal, P. A. S. Lowden, et al.
Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
PNAS, February 18, 2003; 100(4): 2041 - 2046.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. Cepeda, R. S. Hurst, C. R. Calvert, E. Hernandez-Echeagaray, O. K. Nguyen, E. Jocoy, L. J. Christian, M. A. Ariano, and M. S. Levine
Transient and Progressive Electrophysiological Alterations in the Corticostriatal Pathway in a Mouse Model of Huntington's Disease
J. Neurosci., February 1, 2003; 23(3): 961 - 969.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. D. Strand, J. M. Olson, and C. Kooperberg
Estimating the statistical significance of gene expression changes observed with oligonucleotide arrays
Hum. Mol. Genet., September 15, 2002; 11(19): 2207 - 2221.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. Luthi-Carter, A. D. Strand, S. A. Hanson, C. Kooperberg, G. Schilling, A. R. La Spada, D. E. Merry, A. B. Young, C. A. Ross, D. R. Borchelt, et al.
Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects
Hum. Mol. Genet., August 15, 2002; 11(17): 1927 - 1937.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. Y.W. Chan, R. Luthi-Carter, A. Strand, S. M. Solano, S. A. Hanson, M. M. DeJohn, C. Kooperberg, K. O. Chase, M. DiFiglia, A. B. Young, et al.
Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease
Hum. Mol. Genet., August 15, 2002; 11(17): 1939 - 1951.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.