Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's Disease

Ai Yamamoto, Jose J.Lucas, and Rene Hen

Cell 101, 57-66 (2000)


Huntington's disease (HD) is an inherited (autosomal dominant) disorder in which there is progressive neuro-degeneration, affecting the corpus striatum and cerebral cortex of the brain, and for which there is no known cure. Conditional transgenic mice model have been created by using tet-regulatable system therefore could be a powerful means to investigate the relationship of mutant protein and progression of the disease. Mice that expressing a mutated huntingtin developed a neurodegenerative syndrome closely models the human disease. Abolishing expression of the mutant protein not only halts progression of the neuropathology but also reverse aggregate formation and progressive motor decline. The results provide new targets for therapeutic interventions for patients suffering from HD and suggest new therapeutic approaches aimed either to destroy or inactivate the mutant huntingtin protein might be effective.


1. Baron, U., Freundlieb, S., Gossen, M., and Bujard, H. (1995). Co-regulation of two gene activities by tetracycline via a bidirectional promoter. Nucleic Acids Res. 23, 3605-3606.
2. HDCRG (Huntington s Disease Collaborative Research Group). (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington s disease chromosomes. Cell 72, 971-983.
3. Schilling, G., Becher, M.W., Sharp, A.H., Jinnah, H.A., Duan, K., Kotzuk, J.A., Slunt, H.H., Ratovitski, T., Cooper, J.K., and Jenkins, N.A. et al. (1999). Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet. 8, 397-407.