MAP2 AND GAP-43 EXPRESSION IN NORMAL AND WEAVER MOUSE CEREBELLUM - CORRELATIVE IMMUNOHISTOCHEMICAL AND IN-SITU HYBRIDIZATION STUDIES

MAP2 is a major microtubule-associated brain protein, selectively loca lized in dendrites; growth-associated phosphoprotein GAP-43 is a neuro n-specific protein associated with axonal outgrowth, In adult cerebell um, both of these proteins and their corresponding RNA transcripts are most strongly expressed by granule cells. Using immunocytochemistry w ith antibodies and in situ hybridization histochemistry with [P-32] la beled oligonucleotide probes, we examined the cellular localization of MAP2, GAP-43 and their mRNAs in the cerebellum of control and weaver (wv/wv) mutant mice, which exhibit massive granule cell death. In wild -type (+/+) mice, MAP2 immunoreactivity was seen in neuronal somata an d dendrites of the granule cell layer; GAP-43 immunoreactivity was pre sent in molecular layer, corresponding to the distribution of parallel fibres, Transcripts encoding MAP2 and GAP-43 were localized in the la yer of the granule cell somata, In heterozygous weaver mice (wv/+), wh ich feature an intermediate degree of granule cell loss, MAP2 immunore activity was localized in the granular layer, and the pattern of GAP-4 3 immunostaining was also similar to +/+, the only difference being a thinner molecular layer. Heterozygotes had an anatomical pattern of MA P2 and GAP-43 mRNA hybridization qualitatively similar to that of the wild-type with some deviations in signal intensity. In homozygous weav er mutants (wv/wv), MAP2 immunoreactivity was extremely weak in the ar ea beneath Purkinje cells and a certain GAP-43 immunoreactivity was se en in the upper part of cerebellar cortex. Hybridization signals for M AP2 and GAP-43 mRNAs were minimal. The reported alterations in regiona l pattern of MAP2 and GAP-43 expression in mutant mice offer a molecul ar correlate of dendritic and axonal protein gene transcription pertin ent to the neuropathological manifestations of certain forms of heredo degenerative ataxia.