title: Myelination and behaviour of tenascin-C null transgenic mice.
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. [Saga, Y., Yagi, T., Ikawa, Y., Sakakura, T. & Aizawa, S. (1992) Genes Dev., 6 1821-1831] 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.
authors.affiliation: Wellcome/CRC Institute of Developmental Biology and Cancer, Cambridge, UK.
authors.forename: B W
authors.initials: BW
authors.lastname: Kiernan
authors.forename: E
authors.initials: E
authors.lastname: Garcion
authors.forename: J
authors.initials: J
authors.lastname: Ferguson
authors.forename: E E
authors.initials: EE
authors.lastname: Frost
authors.forename: E M
authors.initials: EM
authors.lastname: Torres
authors.forename: S B
authors.initials: SB
authors.lastname: Dunnett
authors.forename: Y
authors.initials: Y
authors.lastname: Saga
authors.forename: S
authors.initials: S
authors.lastname: Aizawa
authors.forename: A
authors.initials: A
authors.lastname: Faissner
authors.forename: R
authors.initials: R
authors.lastname: Kaur
authors.forename: R J
authors.initials: RJ
authors.lastname: Franklin
authors.forename: C
authors.initials: C
authors.lastname: ffrench-Constant
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006579:Heterozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000502:physiology*; D004856:Postural Balance / Q000502:physiology; D012018:Reflex / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology; D013045:Species Specificity; D019063:Tenascin / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*
chemical_list: D004676:Myelin Basic Protein; D019063:Tenascin