Journal of Neuroscience, Vol 2, 1474-1485, Copyright © 1982 by Society for Neuroscience
Granule cell as a site of gene action in the weaver mouse cerebellum: evidence from heterozygous mutant chimeras
D Goldowitz and RJ Mullen
Experimental mouse chimeras were used to determine the site(s) of gene
action in the weaver mutant cerebellum. Chimeras containing mixtures of
heterozygous weaver (wv/+) and non-weaver (+/+) cells were produced by the
standard embryo aggregation technique. The non-weaver component of the
chimera was chosen so that Purkinje cells or granule cells could be
distinguished histologically from weaver Purkinje or granule cells. Levels
of beta-glucuronidase activity were used to mark Purkinje cells, with the
weaver strain having a high beta-glucuronidase activity, while the
non-weaver strain had low beta-glucuronidase activity. The increased
centralized clumping of heterochromatin in ichthyosis (ic) mutant mice
compared to non-ic mice was used to mark granule cell populations. In the
weaver chimera, there was a decreased cerebellar size, decreased numbers of
Purkinje and granule cells, and increased ectopic Purkinje and granule
cells compared to non-weaver, control mice. With the glucuronidase cell
marker, it was found that there was no correlation between ectopia and
genotype; that is, genetically normal cells, as well as weaver cells, were
found in ectopic positions. Thus, the weaver gene acts extrinsic to the
Purkinje cells in creating the ectopia characteristic of heterozygous
weaver mutants. Analysis of the ectopic granule cells, however, revealed
that 100% of the ectopic granule cells were from the weaver component of
the chimera. Thus, the weaver gene intrinsically affects granule cells in
causing ectopia. Other hypothetical sites of gene action would produce a
genetically mixed population of ectopic granule cells, which was not the
case in this study. These findings are discussed in relation to other
abnormalities in the heterozygous weaver mutant and in regard to the
Bergmann glia and homozygous mutant. Finally, speculations on the nature of
the granule cell deficit are discussed briefly.
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