PHENOTYPIC EFFECTS OF THE WEAVER GENE ARE EVIDENT IN THE EMBRYONIC CEREBELLUM BUT NOT IN THE VENTRAL MIDBRAIN

Degeneration of neurons in two structures, the cerabellum and the dopa minergic neurons in the ventral midbrain, is a well characterized acti on of the weaver gene, In order to see whether the gene has effects pr enatally, both the cerebellum and the ventral midbrain were examined i n mouse embryos genotyped for the weaver gene (wv, Girk2) on day E19. Anatomically matched sections of the midline cerebellar vermis were qu antitatively analyzed 2 h after the dams were given a single injection of [H-3]thymidine. A gene-dose effect was seen in the retardation of fissure development. This was more pronounced in homozygotes (wv/wv) a nd less so in heterozygotes (wv/+) when compared with wild type contro ls (+/+). Quantitative measures of the following features showed stepw ise differences between genotypes so that the wv/wv are most affected and wv/+ are somewhat affected compared with +/+ : surface length of t he midline vermis, area of the entire midline vermis and the external germinal layer (egl), total number of cells in the egl, [H-3]thymidine -labeled and -unlabeled egl cells, cells in the Purkinje cell layer, c ells in the region of the deep nuclei, [H-3]thymidine-labeled cells in the Purkinje cell layer (presumptive proliferating Bergmann glia), an d [H-3]thymidine-labeled cells in the region of the deep nuclei. In co ntrast to the obvious phenotypic effects of wv in the embryonic cerebe llum, qualitative immunocytochemical examination of tyrosine hydroxyla se staining in the ventral midbrains of the same embryos showed that t ile position and density of the presumptive dopaminergic neurons was s imilar in all genotypes.