Transgenic models of Huntington's disease

Philos Trans R Soc Lond B Biol Sci. 1999 Jun 29;354(1386):963-9. doi: 10.1098/rstb.1999.0447.

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion. A mouse model of this disease has been generated by the introduction of exon 1 of the human HD gene carrying highly expanded CAG repeats into the mouse germ line (R6 lines). Transgenic mice develop a progressive neurological phenotype with a movement disorder and weight loss similar to that in HD. We have previously identified neuronal inclusions in the brains of these mice that have subsequently been established as the pathological hallmark of polyglutamine disease. Inclusions are present before symptoms, which in turn occur long before any selective neuronal cell death can be identified. We have extended the search for inclusions to skeletal muscle, which, like brain, contains terminally differentiated cells. We have conducted an investigation into the skeletal muscle atrophy that occurs in the R6 lines, (i) to provide possible insights into the muscle bulk loss observed in HD patients, and (ii) to conduct a parallel analysis into the consequence of inclusion formation to that being performed in brain. The identification of inclusions in skeletal muscle might be additionally useful in monitoring the ability of drugs to prevent inclusion formation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Exons
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics*
  • Huntington Disease / physiopathology*
  • Mice
  • Mice, Transgenic
  • Movement Disorders / genetics
  • Movement Disorders / physiopathology
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Peptides / genetics
  • Repetitive Sequences, Amino Acid
  • Trinucleotide Repeats

Substances

  • HTT protein, human
  • Htt protein, mouse
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Peptides
  • polyglutamine