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Journal of Neuroscience, Vol 15, 7953-7965, Copyright © 1995 by Society for Neuroscience
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
AJ Holtmaat, PA Dijkhuizen, AB Oestreicher, HJ Romijn, NM Van der Lugt, A Berns, FL Margolis, WH Gispen and J Verhaagen
Netherlands Institute for Brain Research, Amsterdam-ZO, The Netherlands.
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 that does not
normally express B-50/GAP-43, namely, mature OMP-positive olfactory
neurons. Olfactory neurons have a limited lifespan and are replaced
throughout adulthood by new neurons that migrate into the upper compartment
of the epithelium following their formation from stem cells in the basal
portion of this neuroepithelium. Thus, the primary olfactory 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 nerve fibers in between the juxtaglomerular
neurons or in close approximation to blood vessels were frequently
observed. This suggests that expression of B-50/GAP-43 in mature olfactory
neurons alters their response to signals in the bulb. Other parameters
examined, that is, migration and lifespan of olfactory neurons are normal
in B-50/GAP-43 transgenic mice. These observations provide direct in vivo
evidence for a role of B-50/GAP-43 in nerve fiber formation and in the
determination of the morphology of axons.
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