Decreased expression of striatal signaling genes in a mouse model of Huntington's disease.

@article{LuthiCarter2000DecreasedEO,
  title={Decreased expression of striatal signaling genes in a mouse model of Huntington's disease.},
  author={Ruth Luthi-Carter and Andrew D Strand and N L Peters and Steven M. Solano and Zane R. Hollingsworth and Anil S. Menon and Ariel S. Frey and Boris S. Spektor and Ellen B. Penney and Gabrielle Schilling and Christopher A. Ross and David R. Borchelt and Stephen J. Tapscott and Anne B. Young and Jang-Ho Cha and James M. Olson},
  journal={Human molecular genetics},
  year={2000},
  volume={9 9},
  pages={
          1259-71
        }
}
To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile approximately 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… Expand
Selective deficits in the expression of striatal‐enriched mRNAs in Huntington's disease
TLDR
It is demonstrated that mutant huntingtin protein causes selective deficits in the expression of mRNAs responsible for striatum‐specific physiology and these may contribute to the regional specificity of degeneration observed in HD. Expand
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The findings suggest that htt protein length influences the ability of an expanded polyglutamine domain to alter gene expression and suggests that short N-terminal fragments of mutant htt might be responsible for the gene expression alterations observed in human HD brain. Expand
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TLDR
The data indicate that the dysregulation of calcium homeostasis correlates with changes in the gene expression of members of the calciosome, however, differed in the two models of HD used in this study, indicating that each HD model exhibits distinct features that may only partially resemble the human disease. Expand
In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons.
TLDR
Overall, HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt, in the absence of expression in cortical neurons. Expand
Striatal specificity of gene expression dysregulation in Huntington's disease
  • E. Thomas
  • Biology, Medicine
  • Journal of neuroscience research
  • 2006
TLDR
Large‐scale changes in striatal gene expression in this manner would likely have particularly devastating effects to normal striatal function and could explain the specificity of striatal dysfunction and ultimate neurodegeneration observed in HD. Expand
Gene expression and behaviour in mouse models of HD
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The relationship between gene expression and behaviour in mouse models of HD is important, as this will further knowledge of disease progression and its underlying molecular events, highlight new treatment targets, and potentially provide new biomarkers for therapeutic trials. Expand
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TLDR
These findings identify TrkB as an additional component that potentially might contribute to the altered neurotrophic support in HD and demonstrate that continuous expression of mutant huntingtin is required to down‐regulate TrkB levels. Expand
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