Embryonic stem cells expressing expanded CAG repeats undergo aberrant neuronal differentiation and have persistent Oct-4 and REST/NRSF expression.
作者： Matthew T Lorincz , Peter J Detloff , Roger L Albin , K.Sue O'Shea
DOI: 10.1016/J.MCN.2004.01.016
关键词:
摘要: Nine neurodegenerative disorders are caused by CAG/polyglutamine (polyQ) repeat expansions. The molecular mechanisms responsible for disease-specific neurodegeneration remain elusive. We developed an embryonic stem (ES) cell-based model to probe the role of polyQ tract expansion in neuronal degeneration. ES cells containing expanded CAG repeats hypoxanthine phosphoribosyltransferase (Hprt) gene develop features typical CAG-mediated neuropathology, exhibit length-dependent decrease survival, undergo aberrant differentiation as well persistent Oct-4 and Repressor element-1 transcription factor/neuron restrictive silencer factor (REST/NRSF) expression. This novel will allow analysis pathogenesis degeneration can be used rapidly screen therapeutic interventions these fatal diseases.
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