Role of staggerer gene in determining cell number in cerebellar cortex. II. Granule cell death and persistence of the external granule cell layer in young mouse chimeras.

Staggerer mice (sg/sg) have a severe ataxia correlated with cerebellar Purkinje cell anomalies and granule cell death. Previous studies of adult staggerer----wild-type chimeric mice have revealed that the mutant Purkinje cell defects visible in the light microscope (small size, ectopia and reduced number) are intrinsic properties of sg/sg Purkinje cells, while the granule cell death observed in the mutant is not an intrinsic property of sg/sg granule cells. In this report we continue the study of granule cell death and examine the phenotype, observed in staggerer mutants, of the developmental persistence of the external granular layer (EGL). Four staggerer----wild-type mouse chimeras were examined at 16 or 17 days of postnatal age. Most showed intermediate amounts of granule cell pycnosis and all showed intermediate expression of EGL persistence. There was little correlation observed between the amount of granule cell pycnosis and either the genotype of the immediately underlying Purkinje cells, or the proportion of staggerer cells in the chimera as a whole (determined by the genotype ratio of other brain regions and by coat melanocytes). While the presence or absence of an EGL did not correlate with the genotype of the immediately adjacent Purkinje cells, there was good agreement between the extent of persistence of the EGL and the overall contribution of staggerer cells to the chimera. The results suggest that the intermediate numbers of granule cells observed in adult staggerer chimeras are the result of both reduced granule cell genesis and increased pruning by cell death. The findings are further discussed in terms of two possible models of staggerer gene action.