Developmental Regulation of Myelin-Associated Genes in the Normal and the Myelin Deficient Mutant Rat

Gordon, Marcia N.; Kumar, Sumit; Scully, Sheila; Zhang, M.-S.; Huber, Jean-Pierre; Cole, R.; Vellis, Jean de

doi:10.1007/978-1-4757-5876-4_2

Cited by 18 publications

(14 citation statements)

References 13 publications

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“…results]. The number of GPDH + (immunoreactive) oligodendro cytes , is reduced in 18-to 24-day md brain [5,42], but the reduction in GPDH+ cell num ber (30-50%) is less than the reduction in GPDH mRNA (70-80%) level. Thus, the amount of GPDH mRNA per GPDH-immunoreactive cell must be reduced also.…”

Section: Discussionmentioning

confidence: 98%

Transcriptional Regulation Studies of Myelin-Associated Genes in <i>Myelin-Deficient</i>Mutant Rats

Kumar

Macklin²,

Gordon

et al. 1990

Dev Neurosci

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To identify and assess the consequences of the mutation in myelin-deficient (md) rats, the myelin proteolipid protein (PLP) gene and its expression were studied in md rats. Southern blots of the PLP gene demonstrated that no major deletions or insertions have occurred in this gene. In addition, the mutation in this gene does not result in a splicing defect in the RNAs, since all exons are represented in md PLP RNAs. These data are consistent with results in another laboratory indicating that a point mutation in the PLP gene in md rats results in a single amino acid alteration in the protein. To elucidate the molecular mechanisms producing reduced levels of PLP, myelin basic protein (MBP) and glycerol phosphate dehydrogenase (GPDH) mRNAs, and their corresponding proteins in md rats, in vitro transcription assays were performed. Transcription of the PLP gene in nuclei isolated from 23-day-old md ratbrains was dramatically reduced relative to normal tissue. Thus, the single amino acid alteration in this protein alters the regulation of transcription of this gene. In contrast, the transcriptional activities of the MBP and GPDH genes in md rats were indistinguishable from normal animals. Thus, the lower level of MBP and GPDH mRNA and protein in md rats relative to normal results from a posttranscriptional event.

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Section: Discussionmentioning

confidence: 98%

Transcriptional Regulation Studies of Myelin-Associated Genes in <i>Myelin-Deficient</i>Mutant Rats

Kumar

Macklin²,

Gordon

et al. 1990

Dev Neurosci

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“…Numerous studies have been conducted to evaluate the developmental profile of Plp gene expression in the CNS at both the mRNA [14,15,19,20,55,69,[78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93] and protein [11, 55, 86, 94 -98] levels. The consensus of these studies is that in oligodendrocytes, the peak of Plp gene expression is coincident with the active myelination period of CNS development, which occurs about 3 weeks postnatally in rodents.…”

Section: Temporal Regulation Of Plp Gene Expressionmentioning

confidence: 99%

Where, when and how much: regulation of myelin proteolipid protein gene expression

Wight

Dobretsova

2004

Cellular and Molecular Life Sciences (CMLS)

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The myelin proteolipid protein (PLP) gene ( Plp) encodes the most abundant protein found in myelin from the central nervous system (CNS). Expression of the gene is regulated in a spatiotemporal manner with maximal levels of expression occurring in oligodendrocytes during the active myelination period of CNS development, although other cell types in the CNS as well as in the periphery can express the gene to a much lower degree. In oligodendrocytes, Plp gene expression is tightly regulated. Underexpression or overexpression of the gene has been shown to have adverse effects in humans and other vertebrates. In light of this strict control, this review provides an overview of the current knowledge of Plp gene regulation.

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“…gene expression intrinsically programmed in Pro-OLs, which involves the down-regulation of gene expression facilitating the mitogenic response of OL progenitor cells to growth factors (Hart et al, 1992;Barnett et al, 1995) and the up-regulation of factors controlling myelin gene expression (Collarini et al, 1992;Kim and Hudson, 1992;Haas et al, 1995;Grinspan et al, 1993;Gordon et al, 1990) and proteins that perform posttranslational processing and trafficking functions for the assembly of an intact myelin membrane Huber et al, 1994;Kim et al, 1995;Madison et al, 1996).…”

Section: W H H Krueger Et Almentioning

confidence: 99%

TPO1, a Member of a Novel Protein Family, Is Developmentally Regulated in Cultured Oligodendrocytes

Krueger

Gonye

Madison

et al. 1997

Journal of Neurochemistry

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Although the myelin membrane contains only a small set of major proteins, more sensitive assays indicate the presence of a plethora of uncharacterized proteins. We have used an antibody perturbation approach to reversibly block the differentiation of prooligodendroblasts into myelinating cells, and, in combination with a differential screening procedure, identified novel mRNAs that are activated during this period. One cDNA, TPO1, recognizes a 5.5-kb mRNA that is strongly up-regulated in oligodendrocytes after release of the differentiation block and that is expressed at high levels in brain tissue during active myelination. This cDNA represents at least two mRNAs differing from each other in their 5'-termini. The TPO1 cDNA contains an open reading frame of 1,380 bp, encoding a protein of 51 .8 kDa with a predicted pi of 9.1 that contains two regions homologous to nonclassic zinc finger motifs. Subceilular localization studies suggest the enriched presence of TPO1 in spherical structures along the major cytoplasmic processes of oligodendrocytes. TPO1, along with homologues expressed in testis, placenta, and PC12 cells, form a novel family of proteins with multiple hydrophobic domains possibly serving as membrane spanning regions. We postulate that in oligodendrocytes, TPO1 encodes a protein factor involved in myeiin biogenesis. Key Words: TPO1 -Oligodendrocyte development-Myelin-Zinc finger-Membrane protein-OB-fold.

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Developmental Regulation of Myelin-Associated Genes in the Normal and the Myelin Deficient Mutant Rat

Cited by 18 publications

References 13 publications

Transcriptional Regulation Studies of Myelin-Associated Genes in <i>Myelin-Deficient</i>Mutant Rats

Transcriptional Regulation Studies of Myelin-Associated Genes in <i>Myelin-Deficient</i>Mutant Rats

Where, when and how much: regulation of myelin proteolipid protein gene expression

TPO1, a Member of a Novel Protein Family, Is Developmentally Regulated in Cultured Oligodendrocytes

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