Myelination in the absence of galactolipids and proteolipid proteins

The galactolipids galactocerebroside and sulfatide and the proteolipid protein (PLP) and its splice variant DM20 are the most abundant lipid and protein components of central nervous system myelin. Recent studies have found that mice lacking either the galactolipids or PLP are able to form myelin sheaths with apparently normal periodicity and near normal compaction. Here, we have generated galactolipid/proteolipid double mutants to examine the possibility that these molecules have overlapping functions. We show that the absence of the galactotipids and PLP has pleotropic effects on myelin formation. While oligodendrocytes in the postnatal day 20 galactolipid/proteolipid-deficient mouse are able to elaborate myelin with close to normal intraperiod lines, there is an increased frequency of uncompacted myelin sheaths as well as unmyelinated axons. Moreover, the double mutants display extensive white matter vacuolization of the cerebellum that initiates around postnatal day 16, which correlates with the onset of a severe ataxic phenotype and an increased percentage of apoptotic nuclei in the cerebellar internal granule cell layer. These data indicate that the galactolipids and PLP/DM20 are not required for intraperiod line formation, but they suggest a role for these molecules in mediating myelin compaction and in maintaining the integrity of the cerebellum.