Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mouse myelin proteolipid protein (PLP) gene has been studied in normal and jimpymsd mice. Potential upstream regulatory regions of the normal gene have been cloned and mapped, but when these regions were studied in jimpymsd mice by Southern blots, no alterations were observed, relative to the normal gene. To assess whether the low ratio of PLP to DM20 proteins in this mutant reflected an altered PLP/DM20 ratio mRNAs, S1 nuclease analyses were undertaken, which demonstrated that at all ages studied in both jimpy and jimpymsd mice, PLP mRNA was elevated above DM20 mRNA. When exon 3 (the site of the alternative splice signal for DM20 mRNA) of the jimpymsd PLP gene was sequenced, no mutation was identified. The transcription of the PLP gene in normal and mutant animals was studied. The transcription rate increases in normal animals with development, and in very young jimpymsd or jimpy mice, the transcription rate of the PLP gene was close to that of age-matched normal animals. However, by 10 days of age, the transcription rate of this gene in both mutants was significantly below that of age-matched controls. The transcription rate of the myelin basic protein (MBP) gene was also reduced, indicating that expression of both genes is affected by this mutation. In contrast, the transcription rate of the glycerol phosphate dehydrogenase (GPDH) gene, an early marker of oligodendrocytes, is equal to or greater than normal in both mutants. We have confirmed an earlier report of a point mutation in exon 6 of the jimpymsd PLP gene, which converts an alanine to a valine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutations in the myelin proteolipid protein gene alter oligodendrocyte gene expression in jimpy and jimpymsd mice. 170 30

The myelin-associated proteolipid protein, PLP, is one of the two major components of the central nervous system (CNS) myelin. We analyze, by using a rat PLP cDNA and S1 nuclease protection experiments, the PLP transcripts in the mouse brain and show that the PLP gene encodes two different but related mRNA transcripts, the PLP and the DM-20 transcripts. On the other hand, we demonstrate that in the jimpy mutant, which is characterized by an abnormal CNS myelination, both these transcripts are partially deleted in the 3' end of their coding region. The deletion is 70 (+/- 5) nucleotides long. Implications of this finding for the synthesis of PLP and DM-20 proteins in the mutant are discussed.
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PMID:Myelin proteolipid protein (PLP and DM-20) transcripts are deleted in jimpy mutant mice. 243 45

The gene for the mouse myelin proteolipid protein has been isolated and the seven exons have been sequenced. Since the sequence of a rat proteolipid protein cDNA and partial sequence of the human proteolipid protein gene have been determined, it was possible to demonstrate a very high degree of conservation for the proteolipid protein gene exons among species. While there are some nucleotide changes, the protein coding region of the mouse gene encodes protein that is totally conserved relative to both rat and human proteolipid proteins. The regulatory and noncoding regions of the proteolipid protein gene are also highly conserved. The upstream regulatory and 5'-noncoding region of the gene is 92% homologous to the comparable region of the human proteolipid protein gene, and the 3'-noncoding region of the mouse gene is approximately 90% homologous to a rat proteolipid protein cDNA through 2,200 nucleotides of 3'-noncoding DNA. S1 nuclease protection experiments indicated that the major 5'-end for proteolipid protein mRNAs from mouse, rat, human, or baboon is approximately 147-160 nucleotides upstream from the initial methionine codon of the protein coding region. Other S1 nuclease protection experiments indicated the possible existence of an alternative splice site within exon 3, which may produce mRNA for DM20. This mRNA is approximately 100 nucleotides shorter than that for the proteolipid protein, and it is missing the latter half of exon 3, that is, amino acids 116-150 of the proteolipid protein sequence.
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PMID:Structure and expression of the mouse myelin proteolipid protein gene. 244 35

Transgenic mice containing the early region of the JC virus encoding T-antigen developed neurological disease resulting from dysmyelination in the central nervous system. In this study, we investigate expression of the myelin basic protein (MBP) gene, a major constituent of the myelin sheath, at the RNA level by Northern blot and S1 nuclease assay and at the protein level by Western blot analysis using anti-MBP antibody in two distinct transgenic lines exhibiting different degrees of dysmyelination. Results from Western blot analysis of proteins from the brains of these mice revealed great reductions in MBP levels that parallel the severity of dysmyelination in the corresponding animals. Analysis of MBP RNA by Northern and quantitative S1 assays exhibited no alterations in the transcription initiation sites of the MBP gene in these animals; however, a significant decrease in the level of MBP mRNA was detected, suggesting that T-antigen may negatively influence transcription of the MBP gene. Results from Northern and Western blot analysis of proteolipid protein revealed low-level expression of this gene. Expression of JCV T-antigen is developmentally regulated in the transgenic mice; it appears at 8 days postnatal, peaks at 15 days, and substantially decreases in 18-day-old mice. The programmed expression of JCV T-antigen, which overlaps with MBP gene transcription at the early stage of myelination, suggests the involvement of a pathway which modulates stage-specific regulation of myelin genes and viral gene expression in transgenic mice during brain development.
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PMID:Expression of the myelin basic protein gene in transgenic mice expressing human neurotropic virus, JCV, early protein. 751 1