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 sup erfamily, has been implicated in the formation and maintenance of myel in 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 glycoprotei n prevents axonal regeneration in lesioned nervous tissue. The generat ion of mice deficient in the expression of myelin-associated glycoprot ein by targeted disruption of the mag gene via homologous recombinatio n 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 glycoprot ein involved in the formation and maintenance of myelin in the CNS? an d (ii) does myelin-associated glycoprotein restrict axonal regeneratio n in the adult mammalian CNS? Analysis of optic nerves from mutant mic e revealed a delay in myelination when compared to optic nerves of wil d-type animals, a lack of a periaxonal cytoplasmic collar from most my elin sheaths, and the presence of some doubly and multiply myelinated axons. Axonal regeneration in the CNS of adult myelin-associated glyco protein deficient mice was not improved when compared to wild-type ani mals. These observations indicate that myelin-associated glycoprotein is functionally involved in the recognition of axons by oligodendrocyt es and in the morphological maturation of myelin sheaths. However, res ults do not support a role of myelin-associated glycoprotein as a pote nt inhibitor of axonal regeneration in the adult mammalian CNS.