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

Döbrössy, Máté, Klein, Alexander, Janghra, Narinder, Nikkhah, Guido and Dunnett, Stephen Bruce 2011. Validating the use of M4-BAC-GFP mice as tissue donors in cell replacement therapies in a rodent model of Huntington's disease. Journal of Neuroscience Methods 197 (1) , pp. 6-13. 10.1016/j.jneumeth.2011.01.015

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine
Uncontrolled Keywords: Huntington's disease; striatum; cell transplantation; transgenic BAC mice
Publisher: Elsevier
ISSN: 0165-0270
Last Modified: 04 Jun 2017 03:19

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