Poster Abstracts

Huntington’s disease (HD) is an autosomal dominant disorder\udcaused by expansion of polyglutamine (CAG) repeats in the Huntingtin gene, leading to loss of striatal and cortical neurons\udand deficits in coordinated movements and cognition. Transgenic\udrodent models are valuable for testing cell death mechanisms\udand therapeutic intervention. However, mouse and rat\udmodels may not fully represent the human condition. Induced\udpluripotent stem (iPS) cells, which show striking similarities to\udembryonic stem cells, can now be derived from human adult\udsomatic tissues and have the capacity to be lineage restricted\udinto various neuronal subtypes. More importantly, recent studies\udhave been successful in generating patient specific iPS cells\udfrom a variety of diseases including amyotrophic lateral sclerosis,\udspinal muscular atrophy, Parkinson’s disease, and HD.\udUsing lentiviral mediated over-expression of Oct4, Sox2,\udNanog, Lin28, cMyc and Klf4, we successfully generated iPS\udcell lines from three fibroblast samples: (1) from a 6 year old\udaffected male with 180 CAG repeats, (2) from a 29 year old\udaffected female with 60 CAG repeats, and (3) from a 21 year\udold unaffected female with 33 CAG repeats. We have generated\udstriatal neurons from these three lines in order to determine the\udaffect CAG repeat length has on neuronal health and survival.\udIn order to accelerate these studies a consortium of researchers\udhas been formed who are currently assessing the phenotype of\udneurons generated from these iPS lines. Studies are ongoing\udamongst the consortium members in order to establish a CAGdependent\udHD phenotype in these lines