DIRECTED EXPRESSION OF THE GROWTH-ASSOCIATED PROTEIN B-50 GAP-43 TO OLFACTORY NEURONS IN TRANSGENIC MICE RESULTS IN CHANGES IN AXON MORPHOLOGY AND EXTRAGLOMERULAR FIBER GROWTH/

B-50/GAP-43, a neural growth-associated phosphoprotein, is thought to play a role in neuronal plasticity and nerve fiber formation since it is expressed at high levels in developing and regenerating neurons and in growth cones. Using a construct containing the coding sequence of B-50/GAP-43 under the control of regulatory elements of the olfactory marker protein (OMP) gene, transgenic mice were generated to study the effect of directed expression of B-50/GAP-43 in a class of neurons th at does not normally express B-50/GAP-43, namely, mature OMP-positive olfactory neurons. Olfactory neurons have a limited lifespan and are r eplaced throughout adulthood by new neurons that migrate into the uppe r compartment of the epithelium following their formation from stem ce lls in the basal portion of this neuroepithelium. Thus, the primary ol factory pathway is exquisitely suited to examine a role of B-50/GAP-43 in neuronal migration, lifespan, and nerve fiber growth. We find that B-50/GAP-43 expression in adult olfactory neurons results in numerous primary olfactory axons with enlarged endings preferentially located at the rim of individual glomeruli. Furthermore, ectopic olfactory ner ve fibers in between the juxtaglomerular neurons or in close approxima tion to blood vessels were frequently observed. This suggests that exp ression of B-50/GAP-43 in mature olfactory neurons alters their respon se to signals in the bulb. Other parameters examined, that is, migrati on and lifespan of olfactory neurons are normal in B-50/GAP-43 transge nic mice. These observations provide direct in vivo evidence for a rol e of B-50/GAP-43 in nerve fiber formation and in the determination of the morphology of axons. [Key words: growth-associated protein B-50/GA P-43, olfactory marker protein, olfactory system, transgenic mice, axo n morphology, process formation]