Functional Overlap between the Cell Adhesion Molecule L1 and 440-kD Ankyrin B in Premyelinated Axons

The L1 CAM family of cell adhesion molecules and the ankyrin family of spectrin-binding proteins are candidates to collaborate in transcellular complexes used in diverse contexts in nervous systems of vertebrates and invertebrates. This report presents evidence for functional coupling between L1 and 440-kD ankyrin B in premyelinated axons in the mouse nervous system. L1 and 440-kD ankyrin B are colocalized in premyelinated axon tracts in the developing nervous system and are both down-regulated after myelination. Ankyrin B ( 2 / 2 ) mice exhibit a phenotype similar to, but more severe, than L1 ( 2 / 2 ) mice and share features of human patients with L1 mutations. Ankyrin B ( 2 / 2 ) mice exhibit hypoplasia of the corpus callosum and pyramidal tracts, dilated ventricles, and extensive degeneration of the optic nerve, and they die by postnatal day 21. Ankyrin B ( 2 / 2 ) mice have reduced L1 in premyelinated axons of long fiber tracts, including the corpus callosum, fimbria, and internal capsule in the brain, and pyramidal tracts and lateral columns of the spinal cord. L1 was evident in the optic nerve at postnatal day 1 but disappeared by postnatal day 7 in mutant mice while NCAM was unchanged. Optic nerve axons of ankyrin B ( 2 / 2 ) mice become dilated with diameters up to eightfold greater than normal, and they degenerated by day 20. These findings provide the first evidence for a role of ankyrin B in the nervous system and support an interaction between 440-kD ankyrin B and L1 that is essential for maintenance of premyelinated