The
transplantation of
dopamine-rich tissue into the putamen of patients with
Parkinson's disease shows much potential for use as a therapeutic strategy. However, a number of grafted individuals subsequently developed a set of abnormal
involuntary movements (AIMs), unrelated to the
dyskinesia caused by
L-DOPA treatment, which have been termed graft-induced
dyskinesia. Given the small number of patients, pre-clinical modeling of graft-induced
dyskinesia in animal models will be critical to determine the underlying mechanisms and amelioration potential of this technique. Here we show that abnormal
involuntary movements of the limbs, trunk and face can be observed in transplanted hemi-parkinsonian mice following
amphetamine administration, similar to those previously described to model graft-induced
dyskinesias in rats. C57Bl6 and CD1 mice were first rendered hemi-parkinsonian with
6-hydroxydopamine, treated with
L-DOPA for 21 days until dyskinetic, and then transplanted with a single cell
suspension of embryonic ventral mesencephalon (VM E12.5) tissue from corresponding strains into the denervated striatum. At 16 weeks post-
transplantation, a single injection of
amphetamine-elicited
dyskinesia in a subgroup of mice of both strains, behavioural pattern not observed pre-
transplantation. The number of surviving dopaminergic cells in the graft did not differ between those that developed AIMs and those that did not. The movements were phenotypically comparable to those seen in the rat model and parallels can be drawn to the human form of the movements, although the mouse model maybe less reproducible than the rat equivalent. This mouse model will facilitate assessment of graft-induced
dyskinesia with mouse-derived stem cell lines and exploration of mechanisms using transgenic mice in future studies.