Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington's disease

Behav Brain Res. 2009 Aug 24;202(1):130-7. doi: 10.1016/j.bbr.2009.03.022. Epub 2009 Mar 28.

Abstract

The R6/2 mouse is a popular model of Huntington's disease (HD) because of its rapid progression and measurable behavioral phenotype. Yet current behavioral phenotyping methods are usually univariate (e.g., latency to fall from a rotarod) and labor intensive. We used a force-plate actometer and specialized computer algorithms to partition the data into topographically specific behavioral categories that were sensitive to HD-like abnormalities. Seven R6/2 male mice and 7 wild-type (WT) controls were placed in a 42 cm x 42 cm force-plate actometer for 20-min recording sessions at 6-7, 8-9, 10-11 and 12-13 weeks of age. Distance traveled, number of wall rears, and number of straight runs (traveling 175 mm or more in 1.5s) were reduced in R6/2 relative to WT mice at all ages tested. Low mobility bouts (each defined as remaining continuously in a virtual circle of 15 mm radius for 5s) were increased in R6/2 mice at 6-7 weeks and beyond. Independent of body weight, force off-load during wall rears was reduced in R6/2 mice except at 6-7 weeks. Power spectra of force variation during straight runs indicated an age-related progressive loss of rhythmicity in R6/2 compared to WT, suggesting gait dysrhythmia and dysmetria. Collectively, these data, which extend results obtained with other widely different behavioral phenotyping methods, document a multifaceted syndrome of motor abnormalities in R6/2 mice. We suggest, moreover, that the force-plate actometer offers a high-throughput tool for screening drugs that may affect symptom expression in R6/2 or other HD model mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Algorithms
  • Animals
  • Body Weight
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Disease Progression
  • Fourier Analysis
  • Genotype
  • Humans
  • Huntingtin Protein
  • Huntington Disease / complications
  • Huntington Disease / diagnosis
  • Huntington Disease / psychology*
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Activity*
  • Movement Disorders / diagnosis
  • Movement Disorders / etiology
  • Movement Disorders / psychology
  • Nerve Tissue Proteins / genetics
  • Neuropsychological Tests*
  • Nuclear Proteins / genetics
  • Phenotype
  • Trinucleotide Repeat Expansion

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins