REGIONAL DISTRIBUTION OF AMYLOID BETA-PROTEIN PRECURSOR, GROWTH-ASSOCIATED PHOSPHOPROTEIN-43 AND MICROTUBULE-ASSOCIATED PROTEIN-2 MESSENGER-RNAS IN THE NIGROSTRIATAL SYSTEM OF NORMAL AND WEAVER MUTANT MICE ANDEFFECTS OF VENTRAL MESENCEPHALIC GRAFTS

Using in situ hybridization histochemistry with [P-32]oligonucleotide probes, we studied the cellular localization of RNA transcripts for am yloid beta-protein precursor (betaAPP), growth-associated phosphoprote in-43 (GAP-43) and microtubule-associated protein 2 (MAP2) in the meso striatal system of normal (+/+) and weaver (wv/wv) mutant mice, which lose mesencephalic dopamine neurons. In addition, expression of the sa me messages was studied in ventral mesencephalic cell suspensions tran splanted to the weaver striatum. Transcripts encoding GAP-43, MAP2 and isoforms betaAPP695, betaAPP714 and betaAPP751 were present in normal substantia nigra and progressively reduced in weaver substantia nigra ; such a reduction was correlated with dopamine neuron loss. The survi val of dopamine neurons in unilateral intrastriatal grafts was documen ted by methamphetamine-induced rotational asymmetry tests and by tyros ine hydroxylase immunocytochemistry. High hybridization signals were o btained for GAP-43, MAP2, betaAPP695, betaAPP714 and betaAPP751 RNA tr anscripts in the grafted tissue; the betaAPP770 species-normally seen in striatum and not substantia nigra-was not expressed in the grafts, but it was present in the recipient striatum. Following immunocytochem ical labelling with antibodies, GAP-43 and MAP2 immunoreactivities wer e seen in cell processes in the grafts and surrounding tissue, whereas betaAPP immunoreactivity was mainly found in grafted cell bodies. The se results suggest that the transplanted mesencephalic cells mature ve ry similarly to those in the normal substantia nigra, expressing diffe rent mRNAs that are normally present in the ventral midbrain and which are reduced in the weaver mutant as a consequence of dopamine neuron loss.