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 (13)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Fossale, E.
Right arrow Articles by Persichetti, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fossale, E.
Right arrow Articles by Persichetti, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 19 2233-2241
© 2002 Oxford University Press

Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice

Elisa Fossale, Vanessa C. Wheeler, Vladimir Vrbanac, Lori-Anne Lebel, Allison Teed, Jayalakshmi S. Mysore, James F. Gusella, Marcy E. MacDonald and Francesca Persichetti*

Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA

Received April 10, 2002; Accepted July 18, 2002

The hallmark striatal neurodegeneration of Huntington's disease (HD) is first triggered by a dominant property of the expanded glutamine tract in mutant huntingtin that increases in severity with glutamine size. Indeed 111-glutamine murine huntingtin leads to a dominant cascade of phenotypes in HdhQ111 mice, although these abnormalities are not manifest in HdhQ50 mice, with 50-glutamine mutant protein. Therefore, to identify phenotypes that might reflect events closer to the fundamental trigger mechanism, and that can be measured as a consequence of adult-onset HD mutant huntingtin, we have screened for altered expression of genes conserved in evolution, which are likely to encode essential proteins. Probes generated from HdhQ111 homozygote and wild-type striatal RNAs were hybridized to human gene segments on filter arrays, disclosing a mutant-specific increase in hybridization to Rrs1, encoding a ribosomal protein. Subsequent, quantitative RT–PCR assays demonstrated increased Rrs1 mRNA from 3 weeks of age in homozygous and heterozygous HdhQ111 striatum and increased Rrs1 mRNA expression with a single copy's worth of 50-glutamine mutant huntingtin in HdhQ50 striatum. Moreover, quantitative RT–PCR assays for the human homologue demonstrated elevated Rrs1 mRNA in HD compared with control postmortem brain. These findings, therefore, support a chronic impact of mutant huntingtin on an essential ribosomal regulatory gene to be investigated for its role very early in HD pathogenesis.

* To whom correspondence should be addressed. Tel: +1 6177265726; Fax: +1 6177265736; Email: persiche{at}helix.mgh.harvard.edu


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
 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
 Hum Mol GenetHome page
A. Lloret, E. Dragileva, A. Teed, J. Espinola, E. Fossale, T. Gillis, E. Lopez, R. H. Myers, M. E. MacDonald, and V. C. Wheeler
Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice
Hum. Mol. Genet., June 15, 2006; 15(12): 2015 - 2024.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. Nariai, T. Tanaka, T. Okada, C. Shirai, C. Horigome, and K. Mizuta
Synergistic defect in 60S ribosomal subunit assembly caused by a mutation of Rrs1p, a ribosomal protein L11-binding protein, and 3'-extension of 5S rRNA in Saccharomyces cerevisiae
Nucleic Acids Res., August 12, 2005; 33(14): 4553 - 4562.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
C. M. Everett and N. W. Wood
Trinucleotide repeats and neurodegenerative disease
Brain, November 1, 2004; 127(11): 2385 - 2405.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Gines, E. Ivanova, I.-S. Seong, C. A. Saura, and M. E. MacDonald
Enhanced Akt Signaling Is an Early Pro-survival Response That Reflects N-Methyl-D-aspartate Receptor Activation in Huntington's Disease Knock-in Striatal Cells
J. Biol. Chem., December 12, 2003; 278(50): 50514 - 50522.
[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.