Transgenic Models for Investigating Oligodendrocyte Differentiation and Myelin Formation

Abstract

The myelin membrane is a highly specialized extension of the oligodendroglial plasma membrane, which surrounds axons and forms a tightly compacted multilamellar structure¹. Myelin has a relatively simple protein composition, with the proteolipid (PLP) and DM20 proteins comprising approximately 50% of adult CNS myelin protein^2,3. These proteins are translated from alternatively spliced mRNAs encoded by the PLP gene^4,5,6. Thus, a major portion of the oligodendrocyte differentiation program is dedicated to the expression of the PLP gene. Mutations in this gene are devastating, and animals such as the jimpy mouse or the md rat are severely compromised, dying within the first postnatal month. CNS changes have been noted in these animals, at ages prior to the time of oligodendrocyte differentiation^{7,8,9.10, 11}. In earlier studies, we and others demonstrated that the DM20 mRNA and protein appear prior to PLP in the developing nervous system^{12, 13, 14, 15}. In addition, it has now been shown that the DM20 mRNA is expressed in the developing embryonic nervous system^{16, 17}. Thus, a number of studies have suggested that in addition to the production of the most abundant proteins of the myelin membrane, the PLP gene may encode a protein(s), perhaps the DM20 protein, which is expressed in cells in the developing nervous system prior to oligodendrocyte differentiation.