BACHD transgenic Rat 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.
BACHD rats overexpress full-length human mutant HTT (mHTT) with 97 alternating CAA/CAG repeats on a bacterial artificial chromosome (BAC).
Heterozygous BACHD rats:
- mHTT aggregates
- Motor deficits
- Reversal learning deficits
- Reduced anxiety
- Striatal alterations
Figure 1: RotaRod and Morris water maze. A: RotaRod test was performed from month 1 to 5. Latency to fall off the rod in seconds. B: 7 months old BACHD rats present with a significantly longer latency to find the platform in the reversal trials on day 9 of testing, animals present no learning deficits during the first 8 days of training (data not shown). Two-way ANOVA followed by Bonferroni posthoc test. Mean ± SEM. N = 15 per group. **p<0.01 ***p<0.001.
QPS Austria is ready to provide samples (brain tissue, CSF etc.) from these animals for analyses in your laboratory.
Homozygous BACHD rats:
- Homozygous BACHD rats present the same phenotype as heterozygous BACHD rats but with an earlier disease onset
Figure 2. Passive Avoidance and Barnes Maze test of 2 and 5 months old homozygous BACHD rats, respectively. A: Latency to enter the dark chamber on day 2. B: Latency to enter the target hole during learning and relearning in the Barnes Maze test; C: Latency to enter the target hole during the probe trial (memory) during the Barnes Maze test. Mean ± SEM; A,C: Mann Whitney U-test; B: Two way ANOVA followed by Bonferroni‘s posthoc test. n=16-20 per group; **p<0.01.
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