Nervous system defects of ankyrin(B) (-/-) mice suggest functional overlapbetween the cell adhesion molecule L1 and 440-kD ankyrin(B) in premyelinated axons
P. Scotland et al., Nervous system defects of ankyrin(B) (-/-) mice suggest functional overlapbetween the cell adhesion molecule L1 and 440-kD ankyrin(B) in premyelinated axons, J CELL BIOL, 143(5), 1998, pp. 1305-1315
The L1 CAM family of cell adhesion molecules and the ankyrin family of spec
trin-binding proteins are candidates to collaborate in transcellular comple
xes used in diverse contexts in nervous systems of vertebrates and inverteb
rates. This report presents evidence for functional coupling between L1 and
440-kD ankyrin(B) in premyelinated axons in the mouse nervous system. L1 a
nd 440-kD ankyrin(B) are colocalized in premyelinated axon tracts in the de
veloping nervous system and are both down-regulated after myelination. Anky
rin(B) (-/-) mice exhibit a phenotype similar to, but more severe, than L1
(-/-) mice and share features of human patients with L1 mutations. Ankyrin(
B) (-/-) mice exhibit hypoplasia of the corpus callosum and pyramidal tract
s, dilated ventricles, and extensive degeneration of the optic nerve, and t
hey die by postnatal day 21. Ankyrin(B) (-/-) mice have reduced L1 in premy
elinated axons of long fiber tracts, including the corpus callosum, fimbria
, and internal capsule in the brain, and pyramidal tracts and lateral colum
ns 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) (-/-) 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 axons in vivo.