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© The Rockefeller University Press, 0021-9525/1998//1305 $5.00
The Journal of Cell Biology, Volume 143, Number 5, , 1998 1305-1315

Article

Nervous System Defects of AnkyrinB (–/–) Mice Suggest Functional Overlap between the Cell Adhesion Molecule L1 and 440-kD AnkyrinB in Premyelinated Axons



Paula Scotland*, Daixing Zhou*, Helene Benveniste{ddagger}, and Vann Bennett*

* Howard Hughes Medical Institute and *Departments of Cell Biology, *Biochemistry, {ddagger} Neurobiology, {ddagger}Anesthesiology, and {ddagger}Radiology, Duke University Medical Center, Durham, North Carolina 27710

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 ankyrinB in premyelinated axons in the mouse nervous system. L1 and 440-kD ankyrinB are colocalized in premyelinated axon tracts in the developing nervous system and are both down-regulated after myelination. AnkyrinB (–/–) mice exhibit a phenotype similar to, but more severe, than L1 (–/–) mice and share features of human patients with L1 mutations. AnkyrinB (–/–) 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. AnkyrinB (–/–) 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 ankyrinB (–/–) 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 ankyrinB in the nervous system and support an interaction between 440-kD ankyrinB and L1 that is essential for maintenance of premyelinated axons in vivo.

Key Words: ankyrin • L1 • cell adhesion molecule • mental retardation • gene knock-out

Abbreviations used in this paper: CAM, cell adhesion molecule; DWM, diffusion-weighted MR microscopy; MR, magnetic resonance.

Dr. Beverly Koller is gratefully acknowledged for performing ES cell manipulations as well as advice in design of the targeting construct. Susan Hester of the Duke Microscopy facility performed electron microscopy. Scott Carpenter is acknowledged for technical assistance.

MRM was performed at the Duke Center for In Vivo Microscopy, National Institutes of Health (NIH) National Center for Research Resources No. P41RR05959. This study was funded in part by a grant from the NIH.

Paula Scotland and Daixing Zhou each made major contributions.

Address all correspondence to Vann Bennett, Box 3892, Duke University Medical Center, Durham, NC 27710. Tel.: (919) 684-3538. Fax: (919) 684-3590. E-mail: benne012{at}mc.duke.edu


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