Myelination and behaviour of tenascin-C null transgenic mice

B. W. Kiernan, E. Garcion, J. Ferguson, E. E. Frost, E. M. Torres, S. B. Dunnett, Y. Saga, S. Aizawa, A. Faissner, R. Kaur, R. J.M. Franklin, C. Ffrench-Constant

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Abstract

The extracellular matrix glycoprotein tenascin-C is widely expressed during development and repair, making it surprising that few abnormalities have been found in transgenic mice lacking this molecule. We have therefore re-examined the transgenic mice described by Saga et al. in which tenascin-C was knocked-out by homologous recombination, focusing on two aspects of the nervous system likely to reveal any abnormalities that might follow the loss of tenascin-C. First, we have determined the pattern of myelin and distribution of oligodendrocyte precursor cells in those areas, such as the optic nerve and retina where local concentrations of tenascin-C have been proposed to act as barriers to oligodendrocyte precursor migration and so prevent inappropriate myelination. Secondly, we have examined the behaviour of the mice in a number of well-characterized tests, e.g. beam-walking, passive avoidance and the Morris water maze. We find no abnormalities of myelination or oligodendrocyte precursor distribution in adult mice, showing that local concentrations of tenascin-C are not the sole mechanism responsible for the pattern of myelination in these regions of CNS. However, we do find a number of behavioural abnormalities in these mice and show that hyperlocomotion and deficits in coordination during beam walking can be ascribed to tenascin-C deficiency. The effects on coordination are, however, not seen on a 129 genetic background. Taken together, these results significantly extend the phenotype associated with tenascin-C deficiency but argue against a role in myelination.

Original languageEnglish
Pages (from-to)3082-3092
Number of pages11
JournalEuropean Journal of Neuroscience
Volume11
Issue number9
DOIs
Publication statusPublished - 24 Dec 2001

Keywords

  • Hyperlocomotion
  • Lamina cribrosa
  • Migration
  • Morris water maze
  • Oligodendrocyte precursor
  • Passive avoidance

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