THE CENTRAL PATHWAY OF PRIMARY OLFACTORY AXONS IS ABNORMAL IN MICE LACKING THE N-CAM-180 ISOFORM

Although N-CAM has previously been implicated in the growth and fascic ulation of axons, the development of axon tracts in transgenic mice wi th a targeted deletion of the 180-kD isoform of the neural cell adhesi on molecule (N-CAM-180) appears grossly normal in comparison to wild-t ype mice. We examined the organization of the olfactory nerve projecti on from the olfactory neuroepithelium to glomeruli in the olfactory bu lb of postnatal N-CAM-180 null mutant mice. Immunostaining for olfacto ry marker protein revealed the normal presence of fully mature primary olfactory neurons within the olfactory neuroepithelium of mutant mice . The axons of these neurons form an olfactory nerve, enter the nerve fiber layer of the olfactory bulb, and terminate in olfactory glomerul i as in wild-type control animals. The olfactory bulb is smaller and t he nerve fiber layer is relatively thicker in mutants than in wild-typ e mice. Previous studies have revealed that the plant lectin Dolichos biflorus agglutinin (DBA) clearly stains the perikarya and axons of a subpopulation of primary olfactory neurons. Thus, DBA staining enabled the morphology of the olfactory nerve pathway to be examined at highe r resolution in both control and mutant animals. Despite a normal spat ial pattern of DBA-stained neurons within the nasal cavity, there was a distorted axonal projection of these neurons onto the surface of the olfactory bulb in N-CAM-180 null mutants. In particular, DBA-stained axons formed fewer and smaller glomeruli in the olfactory bulbs of mut ants in comparison to wild-type mice. Many primary olfactory axons fai led to exit the nerve fiber layer and contribute to glomerular formati on. These results indicate that N-CAM-180 plays an important role in t he growth and fasciculation of primary olfactory axons and is essentia l for normal development of olfactory glomeruli. (C) 1997 John Wiley & Sons, Inc.