Analysis of gene action in the meander tail mutant mouse: examination of cerebellar phenotype and mitotic activity of granule cell neuroblasts.
The meander tail (mea) gene results in a stereotypic pattern of cerebellar abnormalities, most notably the virtual depletion of granule cells in the anterior lobe of the cerebellum. The causal basis of this mutation is unknown. In this paper we have taken a three-part approach to the analysis of mea gene action. First, we quantitatively determined the effect of the mea gene on granule cell and Purkinje cell number. We found, in addition to the marked depletion of anterior lobe granule cells ( > 90%), there were also significantly fewer granule cells in the posterior lobe (20-30%) without a concomitant loss of Purkinje cells. Second, we explored the relationship between granule cell depletion caused by the mea gene and by the mitotic poison, 5-fluoro-2'-deoxyuridine (FdU). Prenatal and postnatal ICR mice were treated with FdU to ascertain the regimen that best produces a meander tail-like cerebellar phenotype. The similarity of the effects of the mea gene and injections of FdU at E17 and PO suggests the hypothesis that the mea gene acts to disrupt the cell cycle of cerebellar granule cell precursors. Thus, the third part of this study was to test this hypothesis by using injections of either BrdU (5-bromo-2'-deoxyuridine) or 3H-thymidine into homozygous and heterozygous meander tail littermates at E17 or PO. After processing the tissue for BrdU immunocytochemistry or 3H-thymidine autoradiography, counts were made of the number of labeled and unlabeled external granule layer (EGL) cells to determine the percentage that had incorporated the mitotic label (labeling index). No difference in the labeling index was found between homozygous meander tail mice and normal, heterozygous littermate controls. Therefore, the mitotic activity of the EGL neuroblasts is not disrupted by the mea gene. Furthermore, while a mitotic poison can produce a phenotype similar to the action of the mea gene, mea is phenomenologically different from FdU treatment.
Hamre
K M
KM
Department of Anatomy and Neurobiology, University of Tennessee, Memphis 38163, USA.
Goldowitz
D
D
D000818:Animals; D001345:Autoradiography; D002531:Cerebellum / Q000033:anatomy & histology*; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008938:Mitosis / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype