Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice.

Expanded polyglutamine (polyQ) proteins in Huntington's disease (HD) as well as other polyQ disorders are known to elicit a variety of intracellular toxicities, but it remains unclear whether polyQ proteins can elicit pathological cell-cell interactions which are critical to disease pathogenesis. To test this possibility, we have created conditional HD mice expressing a neuropathogenic form of mutant huntingtin (mhtt-exon1) in discrete neuronal populations. We show that mhtt aggregation is a cell-autonomous process. However, progressive motor deficits and cortical neuropathology are only observed when mhtt expression is in multiple neuronal types, including cortical interneurons, but not when mhtt expression is restricted to cortical pyramidal neurons. We further demonstrate an early deficit in cortical inhibition, suggesting that pathological interactions between interneurons and pyramidal neurons may contribute to the cortical manifestation of HD. Our study provides genetic evidence that pathological cell-cell interactions elicited by neuropathogenic forms of mhtt can critically contribute to cortical pathogenesis in a HD mouse model.

Pubmed ID: 15882643


  • Gu X
  • Li C
  • Wei W
  • Lo V
  • Gong S
  • Li SH
  • Iwasato T
  • Itohara S
  • Li XJ
  • Mody I
  • Heintz N
  • Yang XW



Publication Data

May 5, 2005

Associated Grants

  • Agency: NIA NIH HHS, Id: AG19206
  • Agency: NINDS NIH HHS, Id: NS04739
  • Agency: NINDS NIH HHS, Id: NS049501
  • Agency: NINDS NIH HHS, Id: NS41669

Mesh Terms

  • Animals
  • Blotting, Western
  • Cell Communication
  • Cerebral Cortex
  • Disease Models, Animal
  • Huntington Disease
  • Immunohistochemistry
  • Mice
  • Mice, Mutant Strains
  • Microscopy, Electron, Transmission
  • Mutation
  • Nerve Tissue Proteins
  • Neurons
  • Nuclear Proteins