Purkinje cell loss is due to a direct action of the weaver gene in Purkinje cells: evidence from chimeric mice.
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 beta-glucuronidase activity, Gusb) with C3HAw wild-type embryos (low beta-glucuronidase activity, Gush). Chimeric cerebella were stained for beta-glucuronidase activity and counts were made of the number of wv/- (Gusb) and +/+ (Gush) 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.
Smeyne
R J
RJ
Department of Neurosciences, Roche Institute of Molecular Biology, Memphis, TN.
Goldowitz
D
D
D000818:Animals; D002452:Cell Count; D002531:Cerebellum / Q000166:cytology* / Q000201:enzymology; D002678:Chimera / Q000235:genetics*; D005966:Glucuronidase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000033:anatomy & histology / Q000235:genetics*; D011689:Purkinje Cells / Q000166:cytology* / Q000201:enzymology
D005966:Glucuronidase