Huntingtin inclusions do not down-regulate specific genes in the R6/2 Huntington's disease mouse.

Academic Article


  • Transcriptional dysregulation is a central pathogenic mechanism in Huntington's disease (HD); HD and transgenic mouse models of HD demonstrate down-regulation of specific genes at the level of mRNA expression. Furthermore, neuronal intranuclear inclusions (NIIs) have been identified in the brains of R6/2 mice and HD patients. One possibility is that NIIs contribute to transcriptional dysregulation by sequestering transcription factors. We therefore assessed the relationship between NIIs and transcriptional dysregulation in the R6/2 mouse, using double-label in situ hybridization combined with immunohistochemistry, and laser capture microdissection combined with quantitative real-time PCR. There was no difference in transcript levels of specific genes between NII-positive and NII-negative neurons. These results demonstrate that NIIs do not cause decreases in D2, PPE and PSS mRNA levels in R6/2 striatum and therefore are not involved in the down-regulation of these specific genes in this HD model. In addition, these observations argue against the notion that NIIs protect against transcriptional dysregulation in HD.
  • Published In


  • Animals, Disease Models, Animal, Down-Regulation, Enkephalins, Gene Expression Regulation, Humans, Huntingtin Protein, Huntington Disease, Immunohistochemistry, In Situ Hybridization, Intranuclear Inclusion Bodies, Mice, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Protein Precursors, Receptors, Dopamine D2, Somatostatin
  • Digital Object Identifier (doi)

    Author List

  • Sadri-Vakili G; Menon AS; Farrell LA; Keller-McGandy CE; Cantuti-Castelvetri I; Standaert DG; Augood SJ; Yohrling GJ; Cha J-HJ
  • Start Page

  • 3171
  • End Page

  • 3175
  • Volume

  • 23
  • Issue

  • 12