Jb. Grinspan et al., MATURATION-DEPENDENT APOPTOTIC CELL-DEATH OF OLIGODENDROCYTES IN MYELIN-DEFICIENT RATS, Journal of neuroscience research, 54(5), 1998, pp. 623-634
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.