Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Selective deficits in the expression of striatal-enriched mrnas in huntington's disease

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Desplats, P. A.
  • Kass, K. E.
  • Gilmartin, T.
  • Stanwood, G. D.
  • Woodward, E. L.
  • Head, Steve
  • Sutcliffe, J. Gregor
  • Thomas, Elizabeth

publication date

  • February 2006

journal

  • Journal of Neurochemistry  Journal

abstract

  • We have identified and cataloged 54 genes that exhibit predominant expression in the striatum. Our hypothesis is that such mRNA molecules are likely to encode proteins that are preferentially associated with particular physiological processes intrinsic to striatal neurons, and therefore might contribute to the regional specificity of neurodegeneration observed in striatal disorders such as Huntington's disease (HD). Expression of these genes was measured simultaneously in the striatum of HD R6/1 transgenic mice using Affymetrix oligonucleotide arrays. We found a decrease in expression of 81% of striatum-enriched genes in HD transgenic mice. Changes in expression of genes associated with G-protein signaling and calcium homeostasis were highlighted. The most striking decrement was observed for a newly identified subunit of the sodium channel, beta 4, with dramatic decreases in expression beginning at 8 weeks of age. A subset of striatal genes was tested by real-time PCR in caudate samples from human HD patients. Similar alterations in expression were observed in human HD and the R6/1 model for the striatal genes tested. Expression of 15 of the striatum-enriched genes was measured in 6-hydroxydopamine-lesioned rats to determine their dependence on dopamine innervation. No changes in expression were observed for any of these genes. These findings demonstrate 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.

subject areas

  • Analysis of Variance
  • Animals
  • Calcium
  • Corpus Striatum
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Humans
  • Huntington Disease
  • Immunohistochemistry
  • In Situ Hybridization
  • Medial Forebrain Bundle
  • Mice
  • Mice, Transgenic
  • Microarray Analysis
  • Middle Aged
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
scroll to property group menus

Research

keywords

  • R6/1
  • gene expression
  • human
  • in situ hybridization
  • neurodegeneration
  • striatum
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2005.03588.x

PubMed ID

  • 16405510
scroll to property group menus

Additional Document Info

start page

  • 743

end page

  • 757

volume

  • 96

issue

  • 3

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support