Huntington’s Disease (HD) is a devastating progressive adult-onset neurodegenerative disease. Currently, there is no treatment or a cure for HD. HD is one of the most common familial neurodegenerative disorders, with 30,000 clinically diagnosed HD patients and another 150,000-200,000 at risk for HD in the US. HD progresses relentlessly, usually resulting in death 15-20 years after symptom onset. It is caused by an expansion of a CAG repeat (>35 repeats) in exon 1 of the gene encoding huntingtin, a large highly conserved ubiquitously expressed ~350 kDa protein.
One major focus of the lab is to understand the contribution of the astrocyte to HD pathogenesis. The huntingtin protein is found throughout the nervous system in both neuronal and non-neuronal cells types. However, neurodegeneration seems to only affect a subset of neuronal cell types, most prominently the striatal medium spiny neuron (MSN) and cortical pyramidal neuron. In order to determine which of the cells that express the mutant huntingtin protein significantly contributes to HD pathogenesis, we generated conditional mouse genetic models to mimic aspects of patient pathology and behavior. We use these models to examine behavior and neuropathology in the context of cell-type specific expression of the mutated protein. We believe by focusing on one cell type at a time, we will be able to identify novel mechanisms to target for disease intervention.
