Mice Deficient for Tenascin-R Display Alterations of the Extracellular Matrix and Decreased Axonal Conduction Velocities in the CNS
Open accessAbstract
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 β2 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.
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TN-R−/− mice are TN-R knockout.
“TN-R knockout mice (TN-R−/−)”
From Aggrecan, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress (2014) · cites this paper as [33]
Tenascin-R knockout mice show abnormal perineuronal net staining, with irregular distribution of WFA around soma and dendrites.
“As mentioned above, TN-R knockout mice show abnormal PNN staining, with irregular distribution of WFA around soma and dendrites (Brückner et al., 2000;Morawski et al., 2014;Weber et al., 1999).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Weber et al., 1999
Tnr-deficient mice are phenotypically normal but exhibit a significant decrease in conduction velocity compared with wild-type mice.
“Tnr-deficient mice were phenotypically normal, although they exhibited a significant decrease in conduction velocity as compared with wild-type mice.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Weber et al., 1999
Immunostaining of phosphacan, a high-affinity ligand for TN-R, is weak and diffuse at the nodes in Tnr knockouts compared to wild-type mice.
“Immunostaining of phosphacan, a high-affinity ligand for TN-R, showed it to be weak and diffuse at the nodes in the knockouts when compared to wild-type mice.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Weber et al., 1999
Several extracellular molecules of proteoglycans (e.g., phosphacan) and glycoproteins (e.g., TN-R) localize at the nodes of Ranvier.
“Thereafter, several extracellular molecules of proteoglycans (e.g.phosphacan) and glycoproteins (e.g.TN-R) were found to localize at the nodes of Ranvier (Weber et al., 1999;Ratcliffe et al., 2000).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Weber et al., 1999
Disruption of any single nodal ECM gene does not affect the clustering of nodal Na+ channels.
“Actually, disruption of any single nodal ECM gene does not affect the clustering of nodal Na + channels (Bekku et al., 2010;Dours-Zimmermann et al., 2009;Weber et al., 1999).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Weber et al., 1999
Clustering of nodal sodium channels and paranodal structures appear unaffected in both Vcan V0/V2- and Tnr-deficient mice.
“While the clustering of nodal sodium channels and paranodal structures appear unaffected in both Vcan V0/V2-and Tnr-deficient mice, effect on the conduction velocity is different in the three types of mutants (V0/V2-, Tnr-andHapln2/Bral1-deficient mice), probably due to the differences of degree of disturbed ECM assembly (Bekku et al., 2010;Dours-Zimmermann et al., 2009;Weber et al., 1999).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Weber et al., 1999
The effect on conduction velocity differs among Vcan V0/V2-, Tnr-, and Hapln2/Bral1-deficient mice, probably due to differences in the degree of disturbed ECM assembly.
“While the clustering of nodal sodium channels and paranodal structures appear unaffected in both Vcan V0/V2-and Tnr-deficient mice, effect on the conduction velocity is different in the three types of mutants (V0/V2-, Tnr-andHapln2/Bral1-deficient mice), probably due to the differences of degree of disturbed ECM assembly (Bekku et al., 2010;Dours-Zimmermann et al., 2009;Weber et al., 1999).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Weber et al., 1999
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Self-citation
- Authors
- Weber, P., Bartsch, U., Rasband, M. N., Czaniera, R., Lang, Y., Bluethmann, H., Margolis, R. U., Levinson, S. R., Shrager, P., Montag, D., & Schachner, M.
- Affiliations
- ETH Zurich (CH)
- Universität Hamburg (DE)
- University of Rochester Medicine (US)
- F. Hoffmann-La Roche AG (CH)
- NYU Langone Health (US)
- University of Colorado Denver (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-06-01
- Volume
- 19
- Issue
- 11
- Pages
- 4245-4262
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782606
- OpenAlex
- W2124266106
- Cited by
- 247
- References
- 93
- Citations by year
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- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- Multiple Sclerosis Society
- Deutsche Forschungsgemeinschaft
- Schweizerische Multiple Sklerose Gesellschaft
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- tenascin-R, extracellular matrix, perineuronal nets, nodes of Ranvier, axonal conduction velocity, optic nerve, phosphacan, chondroitin sulfate proteoglycans, interneurons
- MeSH terms
- Animals, Axons, Cells, Cultured, Central Nervous System, Microscopy, Electron, Nerve Net, Nerve Tissue Proteins, Neural Conduction, Optic Nerve, Ranvier's Nodes, Stem Cells, Extracellular Matrix Proteins, Mice, Knockout, Myelin-Associated Glycoprotein, Tenascin, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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