@article{AngelaHodges03152006,
author = {Hodges, Angela and Strand, Andrew D. and Aragaki, Aaron K. and Kuhn, Alexandre and Sengstag, Thierry and Hughes, Gareth and Elliston, Lyn A. and Hartog, Cathy and Goldstein, Darlene R. and Thu, Doris and Hollingsworth, Zane R. and Collin, Francois and Synek, Beth and Holmans, Peter A. and Young, Anne B. and Wexler, Nancy S. and Delorenzi, Mauro and Kooperberg, Charles and Augood, Sarah J. and Faull, Richard L.M. and Olson, James M. and Jones, Lesley and Luthi-Carter, Ruth},
title = {{Regional and cellular gene expression changes in human Huntington's disease brain}},
journal = {Hum. Mol. Genet.},
volume = {15},
number = {6},
pages = {965-977},
doi = {10.1093/hmg/ddl013},
year = {2006},
abstract = {Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative diseases.
},
URL = {http://hmg.oxfordjournals.org/cgi/content/abstract/15/6/965},
eprint = {http://hmg.oxfordjournals.org/cgi/reprint/15/6/965.pdf}
}

@article{Chin-HsingLin01012001,
author = {Lin, Chin-Hsing and Tallaksen-Greene, Sara and Chien, Wei-Ming and Cearley, Jamie A. and Jackson, Walker S. and Crouse, Andrew B. and Ren, Songrong and Li, Xiao-Jiang and Albin, Roger L. and Detloff, Peter J.},
title = {{Neurological abnormalities in a knock-in mouse model of Huntington's disease}},
journal = {Hum. Mol. Genet.},
volume = {10},
number = {2},
pages = {137-144},
doi = {10.1093/hmg/10.2.137},
year = {2001},
abstract = {Mice representing precise genetic replicas of Huntington's disease (HD) were made using gene targeting to replace the short CAG repeat of the mouse Huntington's disease gene homolog (Hdh) with CAG repeats within the length range found to cause HD in humans. Mice with alleles of[~] 150 units in length exhibit late-onset behavioral and neuroanatomic abnormalities consistent with HD. These symptoms include a motor task deficit, gait abnormalities, reactive gliosis and the formation of neuronal intranuclear inclusions predominating in the striatum. This model differs from previously described Hdh knock-ins by its method of construction, longer repeat length and more severe phenotype. To our knowledge, this is the first knock-in mouse model of HD to show increased glial fibrillary acidic protein immunoreactivity in the striatum, suggesting that these mice have neuronal injury similar to that found early in the course of HD. These mice will serve as useful reagents in experiments designed to reveal the molecular nature of neuronal dysfunction underlying HD.
},
URL = {http://hmg.oxfordjournals.org/cgi/content/abstract/10/2/137},
eprint = {http://hmg.oxfordjournals.org/cgi/reprint/10/2/137.pdf}
}

@article{RuthLuthi-Carter05222000,
author = {Luthi-Carter, Ruth and Strand, Andrew and Peters, Nikki L. and Solano, Steven M. and Hollingsworth, Zane R. and Menon, Anil S. and Frey, Ariel S. and Spektor, Boris S. and Penney, Ellen B. and Schilling, Gabriele and Ross, Christopher A. and Borchelt, David R. and Tapscott, Stephen J. and Young, Anne B. and Cha, Jang-Ho J. and Olson, James M.},
title = {{Decreased expression of striatal signaling genes in a mouse model of Huntington's disease}},
journal = {Hum. Mol. Genet.},
volume = {9},
number = {9},
pages = {1259-1271},
doi = {10.1093/hmg/9.9.1259},
year = {2000},
abstract = {To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile ~6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.
},
URL = {http://hmg.oxfordjournals.org/cgi/content/abstract/9/9/1259},
eprint = {http://hmg.oxfordjournals.org/cgi/reprint/9/9/1259.pdf}
}


@article{AlexandreKuhn05212007,
author = {Kuhn, Alexandre and Goldstein, Darlene R. and Hodges, Angela and Strand, Andrew D. and Sengstag, Thierry and Kooperberg, Charles and Becanovic, Kristina and Pouladi, Mahmoud A. and Sathasivam, Kirupa and Cha, Jang-Ho J. and Hannan, Anthony J. and Hayden, Michael R. and Leavitt, Blair R. and Dunnett, Stephen B. and Ferrante, Robert J. and Albin, Roger and Shelbourne, Peggy and Delorenzi, Mauro and Augood, Sarah J. and Faull, Richard L.M. and Olson, James M. and Bates, Gillian P. and Jones, Lesley and Luthi-Carter, Ruth},
title = {{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}},
journal = {Hum. Mol. Genet.},
volume = {16},
number = {15},
pages = {ddm133},
doi = {10.1093/hmg/ddm133},
year = {2007},
abstract = {In order to test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared mRNA changes in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in and full-length transgenic models of HD took longer to appear, 15-month and 22-month CHL2Q150/Q150, 18-month HdhQ92/Q92 and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared to those caused by expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trials.
},
URL = {http://hmg.oxfordjournals.org/cgi/content/abstract/ddm133v1},
eprint = {http://hmg.oxfordjournals.org/cgi/reprint/ddm133v1.pdf}
}

@article{AlexandreKuhn01172008,
author = {Alexandre Kuhn and Ruth Luthi-Carter and Mauro Delorenzi},
title = {Cross-species and cross-platform gene expression studies with the Bioconductor-compliant R package annotationTools},
journal = {BMC Bioinformatics},
volume = {9},
year = {2008},
pages = {26},
url = {http://www.biomedcentral.com/1471-2105/9/26},
}

