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The Journal of Neuroscience, March 15, 2001, 21(6):2039-2047
A Unique Role for Fyn in CNS Myelination
Brian R.
Sperber1, 2,
Éilis A.
Boyle-Walsh1,
Mark J.
Engleka1,
Paul
Gadue1,
Alan C.
Peterson4,
Paul L.
Stein1,
Steven S.
Scherer3, and
F. Arthur
McMorris1, 2
1 The Wistar Institute, Philadelphia, Pennsylvania
19104, 2 Graduate Group in Neuroscience and
3 Department of Neurology, University of Pennsylvania,
Philadelphia, Pennsylvania 19104, and 4 Department of
Neurology and Neurosurgery, Royal Victoria Hospital, McGill University,
Montreal, Canada H3A 1A1
We analyzed the role of Fyn tyrosine kinase in CNS myelination by
using fyn / null mutant mice,
which express no Fyn protein. We found a severe myelin deficit in
forebrain at all ages from 14 d to 1 year. The deficit was maximal
at 1 month of age and was similar regardless of mouse strain background
or whether it was determined by bulk isolation of myelin or by
quantitation of myelin basic protein. To determine the cellular basis
of the myelin deficit, we counted oligodendrocytes in tissue sections
of mice expressing oligodendrocyte-targeted  -galactosidase, and we
used light and electron microscopy to examine the number and morphology
of myelinated fibers and size of myelinated CNS structures. All of
these parameters were reduced in
fyn/ mice. Unexpectedly, there
were regional differences in the myelin deficit; in contrast to
forebrain, fyn/ cervical spinal
cord exhibited no reduction in myelin content, number of
oligodendrocytes, or number of myelinated fibers, nor was myelination
delayed developmentally. We found that oligodendrocytes express Src,
but there was no significant reduction of myelin content in null
mutants lacking the Fyn-related kinases Src, Yes, or Lyn. Finally, we
investigated the molecular features of Fyn that are required for
myelination and found that a single amino acid substitution, which
abolishes the tyrosine kinase activity of Fyn, resulted in a myelin
deficit as great as that observed in the complete absence of Fyn
protein. These results demonstrate that Fyn plays a unique role in
myelination, one that requires its kinase activity.
Key words:
myelin; oligodendrocyte; corpus callosum; spinal cord; tyrosine kinase; Fyn; Src; Lyn; Yes; development; knock-out
Copyright © 2001 Society for Neuroscience 0270-6474/01/2162039-09$05.00/0
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