MATURATION-DEPENDENT APOPTOTIC CELL-DEATH OF OLIGODENDROCYTES IN MYELIN-DEFICIENT RATS

Mutations in the proteolipid protein gene (PLP/plp), which encodes the major intrinsic membrane protein in central nervous system (CNS) myel in, cause inherited dysmyelination in mammals. One of these mutants, t he myelin-deficient (md) rat, has severe dysmyelination that is associ ated with oligodendrocyte cell death. Using the terminal deoxynucleoti dyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) a ssay, which labels apoptotic cells, we find that cell death is increas ed in multiple white matter tracts of md rats. The tracts that myelina te the earliest show the earliest increase in cell death, and cell dea th persists for at least 22 days, the lifespan of these mutant animals . In all tracts, and at all developmental ages examined, apoptotic cel ls expressed the markers of mature oligodendrocytes, such as myelin ba sic protein, myelin-associated glycoprotein, and the Rip antigen, but not chondroitin sulfate proteoglycan, a marker of oligodendrocyte prec ursors. Mature oligodendrocytes fail to accumulate in md brain because they die before they fully mature. (C) 1998 Wiley-Liss, Inc.