The galactolipids galactocerebroside and sulfatide and the proteolipid prot
ein (PLP) and its splice variant DM20 are the most abundant lipid and prote
in components of central nervous system myelin. Recent studies have found t
hat mice lacking either the galactolipids or PLP are able to form myelin sh
eaths with apparently normal periodicity and near normal compaction. Here,
we have generated galactolipid/proteolipid double mutants to examine the po
ssibility that these molecules have overlapping functions. We show that the
absence of the galactotipids and PLP has pleotropic effects on myelin form
ation. While oligodendrocytes in the postnatal day 20 galactolipid/proteoli
pid-deficient mouse are able to elaborate myelin with close to normal intra
period lines, there is an increased frequency of uncompacted myelin sheaths
as well as unmyelinated axons. Moreover, the double mutants display extens
ive white matter vacuolization of the cerebellum that initiates around post
natal 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 f
or these molecules in mediating myelin compaction and in maintaining the in
tegrity of the cerebellum.