Transgenic expression of B-50/GAP-43 in mature olfactory neurons triggers downregulation of native B-50/GAP-43 expression in immature olfactory neurons

The adult mammalian olfactory neuroepithelium is an unusual neural tissue, since it maintains its capacity to form new neurons throughout Life. Newly formed neurons differentiate in the basal layers of the olfactory neuroepit helium and express B-50/GAP-43, a protein implicated in neurite outgrowth, During maturation these neurons migrate into the upper portion of the epith elium, upregulate expression of olfactory marker protein (OMP) and concomit antly downregulate the expression of B-50/GAP-43, Transgenic mice that exhi bit OMP-promoter directed expression of B-50/GAP-43 in mature olfactory neu rons display an unexpected decrease in the complement of B-50/GAP-43-positi ve cells in the lower region of the olfactory epithelium [A.J.G.D. Holtmaat , P.A. Dijkhuizen, A.B. Oestreicher, H.J. Romijn, N.M.T. Van der Lugt, A. B erns, F.L, Margolis, W.H. Gispen, J. Verhaagen, Directed expression of the growth-associated protein B-50/GAP-43 to olfactory neurons in transgenic mi ce results in changes in axon morphology and extraglomerular growth, J. Neu rosci. 15 (1995) 7953-7965]. We have investigated whether the decrement in B-50/GAP-43-positive cells in this region was due to a dislocation of the i mmature neurons to other regions of the olfactory epithelium or to a downre gulation of B-50/GAP-43 synthesis in these immature neurons. In eight of ni ne independent transgenic mouse lines that express the transgene in differe nt numbers or olfactory neurons, a decline in the number of B-50/GAP-43-exp ressing neurons in the basal portion of the olfactory neuroepithelium was o bserved, both at the protein level and the mRNA level. An alternative marke r for immature cells, a juvenile form of tubulin, was normally expressed in this location, indicating that the olfactory epithelium of OMP-B-50/GAP-43 transgenic mice contains a normal complement of immature olfactory neurons and that most of these neurons display a downregulation of B-50/GAP-43 exp ression. (C) 1999 Elsevier Science B.V. All rights reserved.