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, localiz es to nodes of Ranvier and perineuronal nets and interacts in vitro with ot her extracellular matrix components and recognition molecules of the immuno globulin superfamily. To characterize the functional roles of TN-R in vivo, we have generated mice deficient for TN-R by homologous recombination usin g embryonic stem cells. TN-R-deficient mice are viable and fertile. The ana tomy of all major brain areas and the formation and structure of myelin app ear normal. However, immunostaining for the chondroitin sulfate proteoglyca n phosphacan, a high-affinity ligand for TN-R, is weak and diffuse in the m utant when compared with wild-type mice. Compound action potential recordin gs from optic nerves of mutant mice show a significant decrease in conducti on velocity as compared with controls. However, at nodes of Ranvier there i s no apparent change in expression and distribution of Na+ channels, which are thought to bind to TN-R via their beta 2 subunit. The distribution of c arbohydrate 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 i ndicate an essential role for TN-R in the formation of perineuronal nets an d in normal conduction velocity of optic nerve.