OLIGODENDROCYTE DEVELOPMENT AND DIFFERENTIATION IN THE RUMPSHAKER MUTATION

The jimpy rumpshaker (jp(rsh)) mutation is an amino acid substitution in exon 4 (Ile186-->Thr) of the proteolipid protein (PLP) gene on the X chromosome. Affected mice show moderate hypomyelination of the centr al nervous system (CNS) with increased numbers of oligodendrocytes in the white matter of the spinal cord, a feature distinguishing them fro m other PLP mutations such as jp, in which premature cell death occurs with reduced numbers of oligodendrocytes. Myelin sheaths of jp(rsh) i mmunostain for myelin basic protein (MBP) and DM-20, but very few cont ain PLP. This study examines the differentiation of oligodendrocytes c ultured from the spinal cords of young mutant and wild type mice using various surface and cytoplasmic antigenic markers to define the stage of development. The majority of oligodendrocytes from mutant mice pro gress normally to express MBP; approximately 30%, relative to wild typ e, contain DM-20 at the in vivo age of 16 days, but very few immunosta in for PLP or the O10 and O11 markers. The morphology of mutant cells in respect to membrane sheets and processes appears similar to normal. The jp(rsh) oligodendrocyte is, therefore, characterized by a failure to express the markers indicative of the most mature cell; however, i t is probably able to achieve a normal period of survival. These data, taken in conjunction with previous results, suggest that the PLP gene has at least two functions; one, probably involving PLP, is concerned with a structural role in normal myelin compaction; the other, perhap s related to DM-20 (or another lower molecular weight proteolipid), is essential for cell survival. The mutation in jp(rsh) at residue 186 s uggests that this region, which is common to PLP and DM-20, is not cri tical for this latter function. (C) 1993 Wiley-Liss, Inc.