Mesencephalic dopamine cell deficit involves areas A8, A9 and A10 in weaver mutant mice.

Abstract

The mesencephalic dopamine (DA) cell system was examined in mice homozygous and heterozygous for the weaver (wv) gene and in wild-type controls to estimate the extent of cell losses associated with the genetically determined central DA deficiency observed in weaver homozygotes. Animals of the three genotypes (+/+, wv/+, wv/wv) were studied at postnatal day (P)20 and P90. Serial coronal sections were obtained through the brainstem. Half of the sections were immunolabeled with antiserum to tyrosine hydroxylase (TH). Cell counts were obtained in areas A8 (retrorubral nucleus, RRN), A9 (substantia nigra, SN), and A10 (ventral tegmental area, VTA). The counts were analyzed with repeated measures analysis of variance followed by individual comparisons among group means. In A8, weaver homozygotes did not differ significantly from wild-type controls at P20, whereas there was a significant difference of 56% at P90. In A9, weaver homozygotes differed significantly from wild-type mice by 42% at P20 and by 69% at P90. The decrease in cell number between P20 and P90 in weaver homozygotes was 54%. In A10, weaver homozygotes did not differ significantly from wild-type controls at P20, whereas there was a significant difference of 26% at P90. Cell numbers in all three areas of heterozygotes did not differ significantly from wild-type control values at either age point. These findings demonstrate that by three months of age homozygous weaver mutants exhibit nerve cell losses in all three areas of the mesencephalic DA cell system. Such losses account for the DA deficiency seen in striatal, limbic and cortical projection fields.