Mice deficient for tenascin-R display alterations of the extracellular matrix and decreased axonal conduction velocities in the CNS.
Tenascin-R (TN-R), an extracellular matrix glycoprotein of the CNS, localizes to nodes of Ranvier and perineuronal nets and interacts in vitro with other extracellular matrix components and recognition molecules of the immunoglobulin superfamily. To characterize the functional roles of TN-R in vivo, we have generated mice deficient for TN-R by homologous recombination using embryonic stem cells. TN-R-deficient mice are viable and fertile. The anatomy of all major brain areas and the formation and structure of myelin appear normal. However, immunostaining for the chondroitin sulfate proteoglycan phosphacan, a high-affinity ligand for TN-R, is weak and diffuse in the mutant when compared with wild-type mice. Compound action potential recordings from optic nerves of mutant mice show a significant decrease in conduction velocity as compared with controls. However, at nodes of Ranvier there is no apparent change in expression and distribution of Na+ channels, which are thought to bind to TN-R via their beta2 subunit. The distribution of carbohydrate epitopes of perineuronal nets recognized by the lectin Wisteria floribunda or antibodies to the HNK-1 carbohydrate on somata and dendrites of cortical and hippocampal interneurons is abnormal. These observations indicate an essential role for TN-R in the formation of perineuronal nets and in normal conduction velocity of optic nerve.
Weber
P
P
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, CH 8093 Zürich, Switzerland.
Bartsch
U
U
Rasband
M N
MN
Czaniera
R
R
Lang
Y
Y
Bluethmann
H
H
Margolis
R U
RU
Levinson
S R
SR
Shrager
P
P
Montag
D
D
Schachner
M
M
D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000503:physiopathology*; D016326:Extracellular Matrix Proteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018992:Myelin-Associated Glycoprotein / Q000502:physiology; D009415:Nerve Net / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000172:deficiency*; D009431:Neural Conduction / Q000502:physiology*; D009900:Optic Nerve / Q000648:ultrastructure; D011901:Ranvier's Nodes / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D019063:Tenascin / Q000172:deficiency*
D016326:Extracellular Matrix Proteins; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D019063:Tenascin; C074638:tenascin R