Mutant HTT expression leads to a myriad of cellular dysfunctions culminating in neuronal loss and consequent motor, cognitive and psychiatric disturbances in HD patients.
An expansion of glutamine repeats in the N-terminal domain of the huntingtin protein leads to Huntington's disease (HD), a neurodegenerative condition characterized by the presence of involuntary movements, dementia, and psychiatric disturbances.
In contrast, the shortstop mice express an amino-terminal fragment of the mutant Htt protein (exons 1 and 2) and display no behavioral abnormalities or striatal neurodegeneration despite widespread formation of neuronal inclusions.
Mice expressing relatively low steady-state levels of N171 huntingtin with 82 glutamine repeats (N171-82Q) develop behavioral abnormalities, including loss of coordination, tremors, hypokinesis and abnormal gait, before dying prematurely.