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Striatal transplantation in a transgenic mouse model of Huntington's Disease

Dunnett, Stephen Bruce, Carter, R. J., Watts, C., Torres, Eduardo Miguel, Mahal, A., Mangiarini, L., Bates, G. and Morton, A. J. 1998. Striatal transplantation in a transgenic mouse model of Huntington's Disease. Experimental Neurology 154 (1) , pp. 31-40. 10.1006/exnr.1998.6926

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Abstract

Striatal grafts have been proposed as a potential strategy for striatal repair in Huntington's disease, but it is unknown whether the diseased brain will compromise graft survival. A transgenic mouse line has recently been described in which hemizygotes with an expanded CAG repeat in exon 1 of the HD gene exhibit a progressive neurological phenotype similar to the motor symptoms of Huntington's disease. We have therefore evaluated the effects of the transgenic brain environment on the survival, differentiation, and function of intrastriatal striatal grafts and undertaken a preliminary analysis of the effects of the grafts on the development of neurological deficits in the host mice. Hemizygote transgenic and wild-type littermate female mice received striatal grafts at 10 weeks of age and were allowed to survive 6 weeks. Normal healthy grafts were seen to survive and differentiate within the striatum of transgenic mice in a manner comparable to that seen in control mice. The transgenic mice exhibited a progressive decline in body weight from 9 weeks of age and a progressive hypoactivity in an open field test of general locomotor behavior. Although striatal grafts exerted a statistically significant influence on several indices of this impairment, all behavioral effects were small and did not exert any clinically relevant effect on the profound neurological deficiency of the transgenic mice.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0014-4886
Last Modified: 04 Jun 2017 07:33
URI: http://orca.cf.ac.uk/id/eprint/66796

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