Expression of Myelin Proteolipid Protein and Basic Protein in Normal and Dysmyelinating Mutant Mice

Sorg, Barbara A.; Agrawal, Daya; Agrawal, Harish C.; Campagnoni, Anthony T.

doi:10.1111/j.1471-4159.1986.tb12979.x

Cited by 99 publications

(65 citation statements)

References 48 publications

(51 reference statements)

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“…Plp jp mice, which express a mutant form of PLP due to a point mutation in the acceptor splice site of exon 5, have significant alterations in the oligodendrocyte cell cycle, where a high mitotic rate is observed accompanied by significant cell death [29][30][31][32]. Campagnoni's group showed two decades ago that PLP protein and mRNA are dramatically downregulated in Plp jp mice [33][34][35]. Additionally, it has been known for some time that both Plp and Mbp transcriptional activity is decreased in the brains of affected males [5,36].…”

Section: Downregulation Of the Plp Gene And The Plp(+)z Transgene In mentioning

confidence: 99%

Expression of a Myelin Proteolipid Protein (Plp)-lacZ Transgene is Reduced in both the CNS and PNS of Plp jp Mice

et al. 2006

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Jimpy (Plp jp ) is an X-linked recessive mutation in mice that causes CNS dysmyelination and early death in affected males. It results from a point mutation in the acceptor splice site of myelin proteolipid protein (Plp) exon 5, producing transcripts that are missing exon 5, with a concomitant shift in the downstream reading frame. Expression of the mutant PLP product in Plp jp males leads to hypomyelination and oligodendrocyte death. Expression of our Plp-lacZ fusion gene, PLP(+)Z, in transgenic mice is an excellent readout for endogenous Plp transcriptional activity. The current studies assess expression of the PLP(+)Z transgene in the Plp jp background. These studies demonstrate that expression of the transgene is decreased in both the central and peripheral nervous systems of affected Plp jp males. Thus, expression of mutated PLP protein downregulates Plp gene activity both in oligodendrocytes, which eventually die, and in Schwann cells, which are apparently unaffected in Plp jp mice.

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Section: Downregulation Of the Plp Gene And The Plp(+)z Transgene In mentioning

confidence: 99%

Expression of a Myelin Proteolipid Protein (Plp)-lacZ Transgene is Reduced in both the CNS and PNS of Plp jp Mice

et al. 2006

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“…Proteolipid protein (PLP) and 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and their respective mRNA's are equally reduced (Kurihara et al, 1968;Inuzuka et al, 1987;Sorg et al, 1986Sorg et al, , 1987. A discordance between high levels of myelin basic protein (MBP) mRNA compared to lower amounts of MBP have been described (Sorg et al, 1986(Sorg et al, , 1987Carnow et al, 1984;Roth et al, 1985). Reductions in these myelin protein gene prod-ucts are likely to be a result of the pleiotrophic effects common to hypomyelinating mutations and secondary to the primary quaking defect.…”

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confidence: 99%

Endocytic depletion of L-MAG from CNS myelin in quaking mice.

Bø

Quarles

Fujita

et al. 1995

The Journal of Cell Biology

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Abstract. Quaking is an autosomal recessive hypo/dysmyelinating mutant mouse which has a 1-Mbp deletion on chromosome 17. The mutation exhibits pleiotrophy and does not include genes encoding characterized myelin proteins. The levels of the 67-kD isoform of the myelin-associated glycoprotein (S-MAG) relative to those of the 72-kD isoform (L-MAG) are increased in the quaking CNS, but not in other dysmyelinating mutants. Abnormal expression of MAG isoforms in quaking may result from altered transcription of the MAG gene or from abnormal sorting, transport, or targeting of L-MAG or S-MAG. To test these hypotheses, we have determined the distribution of L-MAG and S-MAG in cervical spinal cord of 7-, 14-, 21-, 28-, and 35-d-old quaking mice. In 7-d-old quaking and control spinal cord, L-and S-MAG was detectable in periaxonal regions of myelinated fibers and in the perinuclear cytoplasm of oligodendrocytes. Between 7 and 35 d, L-MAG was removed from the periaxonal membrane of quaking but not control mice. Compared to control mice, a significant increase in MAG labeling of endosomes occurred within oligodendrocyte cytoplasm of 35-d-old quaking mice. S-MAG remained in periaxonal membranes of both quaking and control mice. Analysis of the cytoplasmic domain of L-MAG identifies amino acid motifs at tyrosine 35 and tyrosine 65 which meet the criteria for "tyrosine internalization signals" that direct transmembrane glycoproteins into the endocytic pathway. These results establish that L-MAG is selectively removed from the periaxonal membrane of CNSmyelinated fibers by receptor-mediated endocytosis. The loss of L-MAG from quaking periaxonal membranes results from increased endocytosis of L-MAG and possibly a decrease in L-MAG production.

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“…PLP, another differentiated oligodendrocyte product was reduced in TOG-depleted cells, but this effect could be secondary to the loss of MBP. Mice homozygous for the shiverer mutation are effectively MBP-null mutants and also show a severe reduction in PLP expression (Sorg et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…In homozygous shiverer mice that are MBP-null mutants (Sorg et al, 1986), PLP expression is reduced. To further characterize the TOG knockdown phenotype, PLP levels were analyzed in 6-d-old oligodendrocytes treated at 4 d with TOG shRNA.…”

Section: Tog Shrna Reduces Tog Level In Oligodendrocytes and Impairs mentioning

confidence: 99%

“…MBP mRNA starts to accumulate in oligodendrocytes 3-4 d after their isolation from mixed cultures, and the protein can be detected 1-2 d later (Zeller et al, 1985) (our results). Other myelin-specific proteins, such as proteolipid protein (PLP) and myelin-oligodendrocytic glycoprotein (MOG), follow the same developmental pattern of expression, but, in contrast to MBP, they are synthesized in the oligodendrocyte cell body (Sorg et al, 1986;Holz et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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The Microtubule-Associated Protein Tumor Overexpressed Gene/Cytoskeleton-Associated Protein 5 Is Necessary for Myelin Basic Protein Expression in Oligodendrocytes

Francone¹,

Maggipinto²,

Kosturko³

et al. 2007

J. Neurosci.

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Tumor overexpressed gene (TOG) protein, encoded by cytoskeleton-associated protein CKAP5, is a microtubule-associated protein that binds to heterogeneous nuclear ribonucleoprotein (hnRNP) A2. hnRNP A2 is an RNA trafficking factor that associates with myelin basic protein (MBP) mRNA. In oligodendrocytes, TOG, hnRNP A2, and MBP mRNA colocalize in granules that assemble in the perikaryon and are transported to the peripheral network of processes that extends from it. MBP accumulates preferentially in the membrane of the medial and distal portions of these cellular processes. MBP expression was reduced when TOG level was lowered by short-hairpin (sh) RNA. The reduction in TOG did not affect overall cell morphology or the assembly, transport, localization, or number of MBP mRNAcontaining granules. Reduced levels of TOG did not affect another oligodendrocyte-specific component, myelin oligodendrocyte glycoprotein, which is expressed at the same time as MBP but translated from mRNA localized in the cell body. Expression in a neural cell line of a green fluorescent protein (GFP)-MBP fusion protein derived from a construct containing GFP and the full-length cDNA for the rat 14 kDa MBP was reduced when TOG level was lowered by shRNA treatment. Expression of GFP, derived from GFP mRNA containing the hnRNP A2 binding element of MBP mRNA, was similarly reduced in cells with low TOG levels. These data indicate that TOG is necessary for efficient translation of MBP mRNA and suggest that this role is mediated by its interaction with hnRNP A2.

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Expression of Myelin Proteolipid Protein and Basic Protein in Normal and Dysmyelinating Mutant Mice

Cited by 99 publications

References 48 publications

Expression of a Myelin Proteolipid Protein (Plp)-lacZ Transgene is Reduced in both the CNS and PNS of Plp jp Mice

Expression of a Myelin Proteolipid Protein (Plp)-lacZ Transgene is Reduced in both the CNS and PNS of Plp jp Mice

Endocytic depletion of L-MAG from CNS myelin in quaking mice.

The Microtubule-Associated Protein Tumor Overexpressed Gene/Cytoskeleton-Associated Protein 5 Is Necessary for Myelin Basic Protein Expression in Oligodendrocytes

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