SELECTIVE VULNERABILITY OF LATE-GENERATED DOPAMINERGIC-NEURONS OF THESUBSTANTIA-NIGRA IN WEAVER MUTANT MICE

In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminerg ic substantia nigra neurons degenerate by postnatal day 20, We have no w determined that the total number of dopaminergic neurons in the vent ral midbrains of a litter of obligatory homozygous weaver pups and a l itter of normal wild-type control pups indicates that no significant d ifferences are present between groups at birth, To test the hypothesis that the subsequent degeneration of these neurons is linked to their time of origin, [H-3]thymidine autoradiography was combined with tyros ine hydroxylase immunocytochemistry to construct neurogenetic timetabl es on postnatal day 20 in wild-type mice and weaver homozygotes, Both groups have the same span of neurogenesis but have statistically diffe rent proportions of neurons generated on specific days, In wild-type m ice, more than half of the dopaminergic neurons originate on or after embryonic day 12, In contrast, over two-thirds of the surviving dopami nergic neurons in homozygous weaver mice originate on or before embryo nic day 11. Our data suggest that the weaver gene does not interfere w ith the generation of dopaminergic neurons, but it preferentially kill s late-generated dopaminergic neurons between birth and postnatal day 20.