RT Journal Article
SR Electronic
T1 Severe Hypomyelination of the Murine CNS in the Absence of Myelin-Associated Glycoprotein and Fyn Tyrosine Kinase
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7430
OP 7437
DO 10.1523/JNEUROSCI.20-19-07430.2000
VO 20
IS 19
A1 Karin Biffiger
A1 Susanne Bartsch
A1 Dirk Montag
A1 Adriano Aguzzi
A1 Melitta Schachner
A1 Udo Bartsch
YR 2000
UL http://www.jneurosci.org/content/20/19/7430.abstract
AB The analysis of mice deficient in the myelin-associated glycoprotein (MAG) or Fyn, a nonreceptor-type tyrosine kinase proposed to act as a signaling molecule downstream of MAG, has revealed that both molecules are involved in the initiation of myelination. To obtain more insights into the role of the MAG–Fyn signaling pathway during initiation of myelination and formation of morphologically intact myelin sheaths, we have analyzed optic nerves of MAG-, Fyn- and MAG/Fyn-deficient mice. We observed a slight hypomyelination in optic nerves of MAG mutants that was significantly increased in Fyn mutants and massive in MAG/Fyn double mutants. The severe morphological phenotype of MAG/Fyn mutants, accompanied by behavioral deficits, substantiates the importance of both molecules for the initiation of myelination. The different severity of the phenotype of different genotypes indicates that the MAG–Fyn signaling pathway is complex and suggests the presence of compensatory mechanisms in the single mutants. However, data are also compatible with the possibility that MAG and Fyn act independently to initiate myelination. Hypomyelination of optic nerves was not related to a loss of oligodendrocytes, indicating that the phenotype results from impaired interactions between oligodendrocyte processes and axons and/or impaired morphological maturation of oligodendrocytes. Finally, we demonstrate that Fyn, unlike MAG, is not involved in the formation of ultrastructurally intact myelin sheaths.