R6/2 transgenic Mouse Model

Huntington’s disease (HD) is an autosomal-dominantly inherited, fatal, neurodegenerative disorder. Patients present with motor dysfunction, psychiatric disturbances, cognitive impairments and metabolic abnormalities. The sole cause of developing HD is the expansion of an unstable repeat of CAG base triplets in the coding region of the Huntingtin gene, HTT. CAG repeat lengths of up to 34 are considered to be physiological, while more than 35 CAG repeats lead most likely to the development of HD. The age of disease onset correlates inversely with CAG repeat length and starts at the age of 40–50 years.
R6/2 mice model human Huntington’s disease (HD) by expressing a portion of the human HD gene under human gene promoter elements (1 kb of 5 UTR sequence and exon 1 together with ~120 CAG repeats). Expression of this amino-terminal fragment of the huntingtin protein with its polyglutamine expansion is sufficient to produce the phenotype of human HD. R6/2 mice show:

  • HTT aggregates
  • Reduced activity
  • Motor deficits
  • Learning and relearning deficits
  • Reduced anxiety
  • Neuroinflammation
  • Striatal alterations
  • Neuronal atrophy
  • Mean survival of 100 days

Figure 1 (A): Rota Rod performance of R6/2 mice: motor coordination expressed as time until falling off the rod over age (tg: n = 10; ntg: n = 19); (B) Two Choice Swim Test: percentage of wrong choices during 5 training days (5 trials per day) followed by one reversal day (15 trials, n = 14 per group); two-way ANOVA with Bonferroni`s post hoc test. Mean ± SEM. **p<0.01; ***p<0.001.

 

Figure 2: Astrocytosis in R6/2 mice: R6/2 mice feature increased emergence of astrocytes compared to the ntg control. GFAP (astrocytes, red) plus DAPI (nuclei, blue) in the primary somatosensory cortex and CA1 region of the hippocampus.

 

We would be happy to test your compounds in the R6/2 transgenic mouse model! The most common readouts are:

 

  • Motor deficits
  • Survival
  • Learning and Reversal learning deficits
  • Neuronal atrophy
  • Neuroinflammation
  • polyQ HTT quantification
  • Looking for something else? Please contact us!

 

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