Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, PC06
Generation and characterisation of mouse embryonic stem cell lines for the study of HuntingtonG
S. Gogel1, Y. Pearse1, D. Smith1, G. Bates1
1. Medical and Molecular Genetics, King`s College London, London, United Kingdom.
Huntington's disease (HD) is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamines close to the amino-terminus of the HD protein, huntingtin (htt). HD is characterised neurologically by motor dysfunction, cognitive decline and psychiatric disturbances, which lead to progressive dementia, severe weight loss and death approximately 15-20 years after disease onset. Mutant htt forms intracellular aggregates, and causes selective neurodegeneration of the γ-aminobutyric acid-releasing spiny-projection neurons of the striatum although loss of neurons in many other brain regions has also been reported. We have established mouse embryonic stem cell (ESC) lines from the R6/2 fragment model for HD. Currently we are investigating several protocols for the directed differentiation of the cell lines into neural stem cells (NSC) and neurones. We will evaluate the suitability of the cell lines as in vitro models of HD by determining if they display HD-related phenotypes. Such studies will include the investigation of ESC, NSC and neurones for htt expression, localisation and aggregation, accelerated cell death, transcriptional dysregulation and alterations in neurite outgrowth. Furthermore, ESC derived neurones will be used in our lab in the search for potential therapeutics.
Where applicable, experiments conform with Society ethical requirements