Purkinje cell loss is due to a direct action of the weaver gene in Purkinje cells: evidence from chimeric mice

Abstract

Within the cerebellum of the adult homozygous weaver mutant mouse there is an approximate 50% reduction in the number of vermal Purkinje cells. It is not known if this deficit is due to a primary action of the weaver gene or if the cell loss is due to a secondary effect of the weaver gene. We examined this question using chimeric mice, produced by fusing C57BL/6 homozygous or heterozygous weaver embryos (high P-glucuronidase activity, Gus b ) with C3HA w wild-type embryos (low β-glucuronidase activity, Gus h ). Chimeric cerebella were stained for β-glucuronidase activity and counts were made of the number of wv/− ( Gus b ) and +/+ ( Gus h ) Purkinje cells. If the weaver gene acts intrinsically in the Purkinje cells, then the number of genetically wv/− and not +/+ Purkinje cells should be decreased. Alternatively, if the Purkinje cells are extrinsically affected by the weaver gene, then both wv/− and +/+ should be equally reduced. In this study, using comparative measures of chimerism and Purkinje cell numbers, only weaver Purkinje cells were reduced, while the +/+ Purkinje cells were unaffected in the chimera. These results indicate that the decrease in Purkinje cell number seen in the wv/wv and wv/+ cerebellum is a direct effect of the weaver gene. In concordance with previous work, the disorganization of the Purkinje cells in the cerebellum, however, results from an indirect effect of the weaver gene.