Developmental expression of neural cell type‐specific mRNA markers in the myelin‐deficient mutant rat brain: Inhibition of oligodendrocyte differentiation

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Abstract
We have studied gene expression of neuroglial cell markers in the myelin‐deficient (md) rat brain during postnatal development. Northern blots and slot blots of poly(A)+ RNA from developing brain were sequentially probed with cDNAs specific for the oligodendrocyte markers glycerol phosphate dehydrogenase (GPDH), myelin basic protein (MBP), and proteolipid protein (PLP), for the neuronal marker glutamic acid decarboxylase (GAD), and for the astrocyte markers glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). GPDH mRNA levels were also examined in two peripheral tissues, liver, and skeletal muscle (hindlimb). Despite a lack of CNS myelin in the md mutant, transcripts of all oligodendroglial markers were detectable except the 1.6‐kb PLP message. Brain GPDH mRNA levels were initially equivalent in md and unaffected littermates at postnatal day 15 (PI5), but the mutants failed to display the normal developmental increase in gene expression. By P25, GPDH mRNA expression in md rat brain was approximately 20% of control levels. GPDH mRNA expression in peripheral tissues was less affected than in brain and was lower in md mutants only at the later developmental ages. Expressions of GAD, GFAP, and GS mRNAs in developing md rat brain were not altered. The mRNA levels of the two myelin markers, MBP and PLP, were severely impaired in md rat brain during the entire myelinating period and represented less than 10% of control mRNA levels at P25. The most important observation was that the large PLP transcript (3.2 kb) was slightly shorter in size in md rat brain as compared to normals. These data indicate that the md mutation does not affect the normal development of astrocytes or GABAergic neurons but severely inhibits the normal differentiation of oligodendrocytes, possibly because of an alteration in the PLP mRNA.