ATROPHY AND LOSS OF DOPAMINERGIC MESENCEPHALIC NEURONS IN HETEROZYGOUS WEAVER MICE

The phenotypic effect of the weaver mutation in the ventral midbrain o f homozygous mutants is associated with the progressive loss of dopami nergic neurons. To discover whether the number of mesencephalic dopami nergic cells is altered in weaver heterozygotes (wv/+), we studied mic e between 20 and 365 days of age. We counted tyrosine hydroxylase (TH) -immunopositive cells in the substantia nigra (SN), retrorubral nucleu s (RRN), and ventral tegmental area (VTA), and measured cross-sectiona l areas of neuronal somata in the SN of wv/+ and age-matched wild-type controls (+/+). The number of TH-positive cells in the wv/+ ventral m idbrain was on average 13% lower than normal. Cell loss was detected s electively in the SN (12%) and VTA (23%). The areas of somatic profile s in the wv/+ nigral neurons were on average reduced by 9.8%. The neur onal losses in the SN and VTA correlated with a 13.8% reduction in dop amine level in the ventral striatum in wv/+ mice at 14-16 months of ag e. Our findings imply that a single dose of the weaver gene in the mou se is associated with cellular damage leading to a chronic deficiency in the mesostriatal dopaminergic system.