Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. It is characterized by motor disturbance, cognitive loss and psychiatric manifestations. The disease typically starts in midlife and symptoms progress over the course of 15-20 years until death. The mutation responsible for HD is an unstable expansion of CAG repeats in the gene encoding Huntington. PsychoGenics has experience in testing a number of models for HD, including the ability to provide services in the R6/2 transgenic mouse model (see Press Release). The R6/2 model is the first developed and most widely used transgenic model for HD. It carries exon-1 of mutant human huntingtin gene, and mice used in testing have around ~120 CAG repeats. The Phenotype includes changes in body weight, declines in open field activity, rotarod performance, and cognitive deficits and is first observed at around 5 - 6 weeks of age with a median premature death at ~ 16 - 18 weeks of age. Neuropathology associated with the model includes neuronal intranuclear inclusions and cellular dysfunction.

Motor coordination and exercise capacity are assessed by rotarod. Tests are performed on separate days, with multiple trials per day. Mice are placed on the rotarod and the speed is gradually and uniformly increased in speed over a maximum period of time. The time that each mouse remains on the rotating rod before falling 20 cm is recorded.

Impaired Rotarod performance observed in R6/2 mice compared with wild type littermates with significant differences observed between the mutant R6/2 mice and their Wild Type (WT) littermates as early as 6 weeks of age.

Rearing-climbing behavior is used to assess motor movement and coordination. The mouse is placed on a flat surface and a closed-top wire mesh cylinder 15 cm X 20 cm tall is placed over the mouse. The animal's behavior is videotaped and latency to climb is measured over a 5 min period.

The open field test (OF) is used to assess both anxiety-like behavior and motor activity. The enclosure is configured to split the open field into a center and periphery zone. Animals having higher levels of anxiety or lower levels of activity tend to stay in the corners of the OF enclosures. Mice that have high levels of activity and low levels of anxiety tend to spend more time in the center of the enclosure.

The formation of contextual or cued memories is dependent upon the integrity of medial temporal lobe structures such as the hippocampus and amygdala respectively. In this assay mice are trained to remember that a particular salient context (conditioned stimulus; CS) is associated with an aversive event, in this case a mild foot shock (the unconditioned stimulus, US). Animals that show good learning freeze upon re-presentation of the context (Contextual Fear Conditioning) or the tone (Cued Fear Conditioning).

The swim tank is a simple learning protocol where mice learn to escape an aversive water environment by climbing onto a platform. The location of the platform is signaled by a cue (light) at one end of the aquarium, so mice need to learn to associate the cue with the position of the platform. Mice are placed in the center of a water-filled aquarium and the choice of direction towards the platform is recorded.