AMELIORATION OF THE BEHAVIORAL-PHENOTYPE IN WEAVER MUTANT MICE THROUGH BILATERAL INTRASTRIATAL GRAFTING OF FETAL DOPAMINE CELLS

Weaver mutant mice lose more than two-thirds of their nigral dopamine neurons. Behaviorally, weaver homozygotes display tremor, gait instabi lity, and toppling over to the sides after a few steps. The recovery o f functional responses was determined in a battery of behavioral tests in weaver mutants after bilateral transplantation of mesencephalic ce ll suspensions (prepared from wild-type mice) to the striatum. Equilib rium was tested by the time mice were able to stay on a suspended bala nce rod before falling off. Locomotor coordination was measured by the number of times mice toppled over to the sides as they moved about in an open-field matrix. Locomotor activity was quantified by the number of square crossings in an open-field matrix. Grafted weaver mutants p erformed significantly better than non-grafted mutant mice in all of t hese three tasks. The findings clearly demonstrate that bilateral tran splants of foetal DA cells enhance motor performance in the weaver mod el of chronic nigrostriatal DA deficiency.