Elimination of Bax expression in mice increases cerebellar purkinje cell numbers but not the number of granule cells.

Cerebellar Purkinje cells and granule cells have been studied extensively as models for investigating neuron-target interactions and the regulation of cell numbers in the developing central nervous system. Recent studies of transgenic mice that overexpress a human Bcl-2 transgene in Purkinje cells suggest both that programmed cell death plays an unexpected role in regulating Purkinje cell number and that Purkinje cells influence the number of granule cells. The role of cell death-related proteins and Purkinje-granule cell interactions in cerebellar development was investigated further in this study by counting the number of Purkinje and granule cells in knockout mutants with a deletion in the proapoptotic gene, Bax. The total number of Purkinje cells was estimated using stereological counting principles in six adult wild type mice, four hemizygous Bax +/- controls, and six Bax -/- knockout mutants. The total number of granule cells per cerebellum was estimated in three adult wild type mice, three hemizygous Bax +/- controls, and three Bax -/- knockout mutants. The number of Purkinje cells increased significantly by over 30% in the Bax -/- knockout mutants compared with wild type and hemizygote controls, whereas the number of granule cells was unchanged in the Bax -/- mutants. There was no change in the volume of the cerebellar cortex or in the size of Purkinje cell bodies in the Bax -/- mutants, implying that Purkinje cell density was increased in the Bax -/- mutants. The increase in Purkinje cell numbers in the Bax -/- knockout mice supports previous evidence that Purkinje cells undergo a period of naturally occurring cell death that is mediated at least in part by the cell death proteins Bcl-2 and Bax. The lack of an effect of Bax gene expression on granule cell numbers indicates that Bax is not an obligate participant in naturally occurring cell death in granule cells.