GENE-EXPRESSION AND OLIGODENDROCYTE DEVELOPMENT IN THE MYELIN-DEFICIENT RAT

The proteolipid proteins play a major role in the structure of the CNS myelin sheath, but they have also been implicated in the oligodendroc yte development leading to myelination, Mutations in the PLP gene resu lt in severe dysmyelination and a paucity of mature oligodendrocytes, The myelin deficient (md) rat, carrying a Thr75-->Pro substitution pre sent in both isoforms of proteolipid protein (PLP and DM20), is the mo st severely affected of the PLP mutants described to date. The express ion of myelin associated genes was quantitated to determine the effect of the mutation on oligodendrocyte development in vivo. At 5 days pos tnatal, gene expression in the md rat approximated that in age-matched control rats, but as they matured, there was a progressive inhibition of gene expression in the md rats, The genes expressed late in the my elination program (PLP and MBP) were affected more dramatically than t hose expressed earlier in oligodendrocyte development (CNP and GPDH), The results indicate that the later stages of oligodendrocyte maturati on and myelin elaboration are inhibited. (C) 1995 Wiley-Liss, Inc.