Early postnatal changes of the dopaminergic mesencephalic neurons in the weaver mutant mouse.

In adult weaver (wv) mutant mice up to 70% of the mesostriatal dopaminergic neurons are lost and major alterations of the dopaminergic dendrites of the substantia nigra have been described. We sought to determine the time of onset of these alterations. Cell counts of the main dopaminergic (DA) mesencephalic cell groups (A8, A9, A10), as labeled with tyrosine hydroxylase immunocytochemistry were done in wild-type and homozygous wv/wv pups. No loss of the DA neurons, was detectable at postnatal day 7 (P7), while reductions in substantia nigra (and retrorubral area) amounted to 35% at P14 and 47% by P21. On the other hand, the severe reduction of dopaminergic dendrites, particularly of their distal compartments was already visible from P3 on. During the first postnatal week, this was associated to abnormal clustering of the dopaminergic neurons. These early neuritic alterations were present, though to a milder degree, in heterozygous (wv/+) mice.