The weaver gene continues to target late-generated dopaminergic neurons in midbrain areas at P90

To determine if lethal action of the weaver gene is more intense in late-generated dopaminergic neurons in midbrain areas on postnatal day (P) 90 [3H] thymidine autoradiography and tyrosine hydroxylase immunohistochemistry were combined in the same tissue section in homozygous weaver mice and normal controls. The experimental animals were the offspring of pregnant dams injected with [3H] thymidine on embryonic days (E) 11-12, E12-13, E13-14 and E14-15. Neurogenetic timetables of dopaminergic neurons were different between wild type and homozygous weavers in all midbrain areas analyzed. A substantial number of late-generated neurons in the substantia nigra pars compacta and in the ventral tegmental area are missing at P90, in these dopaminergic areas the loss is greater than at P20 indicating that neuronal loss is progressive. The greatest loss is in the substantia nigra pars compacta, confirming the report of Bayer et al. [Exp. Brain Res. 105 (1995) 200] at P20, while in the retrorubral field and the interfascicular nucleus late-generated neuron loss was less severe. These results furnish more evidence that dopaminergic neuron loss in homozygous weaver midbrain is a phenomenon linked to development. (C) 2000 Elsevier Science B.V.