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

Ruth Luthi-Carter, Andrew Strand, Nikki L. Peters, Steven M. Solano, Zane R. Hollingsworth, Anil S. Menon, Ariel S. Frey, Boris S. Spektor, Ellen B. Penney, Gabriele Schilling, Christopher A. Ross, David R. Borchelt, Stephen J. Tapscott, Anne B. Young, Jang Ho J. Cha, James M. Olson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1259-1271
Number of pages13
JournalHuman molecular genetics
Volume9
Issue number9
DOIs
StatePublished - May 22 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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