Myelination and behaviour of tenascin-C null transgenic mice.
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.
Kiernan
B W
BW
Wellcome/CRC Institute of Developmental Biology and Cancer, Cambridge, UK.
Garcion
E
E
Ferguson
J
J
Frost
E E
EE
Torres
E M
EM
Dunnett
S B
SB
Saga
Y
Y
Aizawa
S
S
Faissner
A
A
Kaur
R
R
Franklin
R J
RJ
ffrench-Constant
C
C
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*
D004676:Myelin Basic Protein; D019063:Tenascin