Myelination and axonal regeneration in the central nervous system of mice deficient in the myelin-associated glycoprotein.
The myelin-associated glycoprotein, a member of the immunoglobulin superfamily, has been implicated in the formation and maintenance of myelin sheaths. In addition, recent studies have demonstrated that myelin-associated glycoprotein is inhibitory for neurite elongation in vitro and it has therefore been suggested that myelin-associated glycoprotein prevents axonal regeneration in lesioned nervous tissue. The generation of mice deficient in the expression of myelin-associated glycoprotein by targeted disruption of the mag gene via homologous recombination in embryonic stem cells has allowed the study of the functional role of this molecule in vivo. This review summarizes experiments aimed at answering the following questions: (i) is myelin-associated glycoprotein involved in the formation and maintenance of myelin in the CNS? and (ii) does myelin-associated glycoprotein restrict axonal regeneration in the adult mammalian CNS? Analysis of optic nerves from mutant mice revealed a delay in myelination when compared to optic nerves of wild-type animals, a lack of a periaxonal cytoplasmic collar from most myelin sheaths, and the presence of some doubly and multiply myelinated axons. Axonal regeneration in the CNS of adult myelin-associated glycoprotein deficient mice was not improved when compared to wild-type animals. These observations indicate that myelin-associated glycoprotein is functionally involved in the recognition of axons by oligodendrocytes and in the morphological maturation of myelin sheaths. However, results do not support a role of myelin-associated glycoprotein as a potent inhibitor of axonal regeneration in the adult mammalian CNS.
Bartsch
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Department of Neurobiology, Swiss Federal Institute of Technology, Zürich, Switzerland.
D000818:Animals; D001369:Axons / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000235:genetics*; D009416:Nerve Regeneration / Q000502:physiology*
D018992:Myelin-Associated Glycoprotein