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Publication : Validating the use of M4-BAC-GFP mice as tissue donors in cell replacement therapies in a rodent model of Huntington's disease.

First Author  Döbrössy M Year  2011
Journal  J Neurosci Methods Volume  197
Issue  1 Pages  6-13
PubMed ID  21295605 Mgi Jnum  J:351339
Mgi Id  MGI:7663071 Doi  10.1016/j.jneumeth.2011.01.015
Citation  Dobrossy M, et al. (2011) Validating the use of M4-BAC-GFP mice as tissue donors in cell replacement therapies in a rodent model of Huntington's disease. J Neurosci Methods 197(1):6-13
abstractText  Huntington's disease (HD) is a neurodegenerative disease with currently only symptomatic treatment. Cell-based therapy, aiming at replacing the lost medium spiny neurons (MSN) with primary fetal striatal cells, has had some success at modifying the symptoms both in experimental studies and clinical trials. Additional pre-clinical studies are required to optimise transplantation protocols and conditions, learn about the limits of circuit reconstruction and functional recovery, and test alternative cell sources. Transgenic mice with integrated bacterial artificial chromosome (BAC) expressing the green fluorescent protein (GFP) can be used to study specific neuronal projections. The BAC transgenic line used in this study, with the GFP expression under the control of the muscarinic receptor M4 promoter, selectively expressed the reporter gene in the direct efferent pathway of the MSN projecting from the striatum to the substantia nigra pars reticulata and the entopeduncular nucleus, the rodent equivalent of the internal segment of the globus pallidus. The current work was designed to validate the use of M4-BAC-GFP mice as tissue donors in cell-based therapy in a rodent model of HD by examining the effect of the transplantation procedure on the GFP expression; the feasibility of identifying the GFP expression in vivo after different time points; and the survival and integration of the transgenic striatal tissue transplant up to 6 months in the host. The data confirm that embryonic striatal tissue from the M4-BAC-GFP mice survives, stably expresses GFP, and thus represents a powerful novel way to study graft-host interaction in this animal model neurodegeneration.
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