Mouse Model Reveals Molecular Basis for Huntington's Disease

Huntington's disease occurs at a frequency of five to seven per hundred thousand, and some relatives of affected individuals have a 50% risk of inheriting the mutation responsible. Investigators at the Emory University School of Medicine (Atlanta, GA, USA) developed a mouse model for Huntington's disease by knocking out the gene that produces huntington-associated protein-1 (HAP1), which is involved in intracellular trafficking of epidermal growth factor receptor (EGFR) and is highly expressed in the hypothalamus.


Mice lacking HAP1 died prematurely due to suppression of appetite and failure to feed. Electron micrographs of the hypothalamus from these animals revealed the degeneration in hypothalamic regions that control feeding behavior. A second mouse model with overexpression of HAP1 showed similar degeneration in the hypothalamus. These findings were published in the July 30, 2003, issue of the Journal of Neuroscience.

Senior author Dr. Xiao-Jiang Li, associate professor of human genetics at Emory University, explained, " Previously, scientists could not find neurodegeneration in mice similar to what is present in Huntington's patients. This could be because mice do not live long enough for us to observe effects in the basal ganglia, or it could be because of their early death caused by artificial overproduction of the mutant proteins. But our research confirms that the mouse model works well for the hypothalamus and that HAP-1 loss of function is involved.”




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