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

Striatal grafts have been proposed as a potential strategy for striatal rep air in Huntington's disease, but it is unknown whether the diseased brain w ill compromise graft survival. A transgenic mouse line has recently been de scribed in which hemizygotes with an expanded CAG; repeat in exon 1 of the HD gene exhibit a progressive neurological phenotype similar to the motor s ymptoms of Huntington's disease. We have therefore evaluated the effects of the transgenic brain environment on the survival, differentiation, and fun ction of intrastriatal striatal grafts and undertaken a preliminary analysi s of the effects of the grafts on the development of neurological deficits in the host mice. Hemizygote transgenic and wild-type littermate female mic e 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 con trol mice. The transgenic mice exhibited a progressive decline in body weig ht from 9 weeks of age and a progressive hypoactivity in an open held test of general locomotor behavior. Although striatal grafts exerted a statistic ally significant influence on several indices of this impairment, all behav ioral effects were small and did not exert any clinically relevant effect o n the profound neurological deficiency of the transgenic mice. (C) 1998 Aca demic Press.