FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1481210380> ?p ?o ?g. }

• W1481210380 abstract "Mutations in proteolipid protein 1 (PLP1), an X-linked gene causes Pelizaeus-Merzbacher disease (PMD) in humans. The most frequent cause of PMD is the duplication of PLP1, which encodes the major myelin membrane protein of the human CNS. The #66 transgenic mice with extra copies of the wild type Plp1 gene are a valid model of PMD caused by increased gene dosage (Readhead et al., 1994). These mice develop dysmyelinating or demyelinating phenotypes dependant on the gene dosage. This study investigated the effects of both low and high increased Plp1 gene dosage on various different selected aspects of myelin, including morphology, message and protein levels of PLP/DM20 and other representative myelin proteins and PLP/DM20 dynamics. Early in development mice with low increased gene dosage (hemizygous) are indistinguishable at the protein and myelin levels from their wild type littermates. During myelination these animals display elevated levels of PLP/DM20 in the oligodendrocyte cell body and alterations in other myelin protein levels and to the structure of myelin but these are transitory effects. These transient changes suggest the oligodendrocytes at low gene dosage retain the ability to regulate expression, production and incorporation of proteins into myelin thus maintaining the normal process of myelination. At high increased gene dosage (homozygous), oligodendrocytes in culture, pre and early myelinating oligodendrocytes in vivo and oligodendrocytes in vivo during peak myelination all exhibit elevated levels of PLP/DM20 in the their cell bodies. The protein is sequestered into autophagic vacuoles and late endosomes/lysosomes (LE/Ls), while the levels in myelin are reduced compared to wild type and hemizygous cells. Synthesis, partitioning with lipids and incorporation of PLP/DM20 are all also affected in the homozygous animals. The increased Plp1 gene dosage does affect other myelin proteins, in particular MBP, which showed a consistent and dramatic reduction in oligodendrocytes and myelin. These results indicate the heterogeneity of phenotypes and underlying changes caused by low and high increased Plp1 gene dosage. The cause of the dysmyelination observed in #66 mice and patients with PMD does not appear to be due to one single change in myelinogenesis. Each alteration observed in #66 transgenic mice could be a contributing factor. Importantly, the perturbation of MBP expression, in the light of this gene’s pivotal role in myelination, highlights that the relationship between Plp1 and Mbp expression is implicated in the pathogenesis of dysmyelination." @default.
• W1481210380 created "2016-06-24" @default.
• W1481210380 creator A5049352059 @default.
• W1481210380 date "2007-01-01" @default.
• W1481210380 modified "2023-09-24" @default.
• W1481210380 title "The effects of increased Plp1 gene dosage on expression and processing of myelin proteins" @default.
• W1481210380 cites W117390725 @default.
• W1481210380 cites W1591432909 @default.
• W1481210380 cites W1973556228 @default.
• W1481210380 cites W1991144796 @default.
• W1481210380 cites W2013404388 @default.
• W1481210380 cites W2030241802 @default.
• W1481210380 cites W2053130559 @default.
• W1481210380 cites W2055154551 @default.
• W1481210380 cites W2075344467 @default.
• W1481210380 cites W2078253619 @default.
• W1481210380 cites W2085453035 @default.
• W1481210380 cites W2126969864 @default.
• W1481210380 cites W2129000774 @default.
• W1481210380 cites W2133403068 @default.
• W1481210380 cites W2151464048 @default.
• W1481210380 hasPublicationYear "2007" @default.
• W1481210380 type Work @default.
• W1481210380 sameAs 1481210380 @default.
• W1481210380 citedByCount "0" @default.
• W1481210380 crossrefType "dissertation" @default.
• W1481210380 hasAuthorship W1481210380A5049352059 @default.
• W1481210380 hasConcept C102230213 @default.
• W1481210380 hasConcept C104317684 @default.
• W1481210380 hasConcept C134018914 @default.
• W1481210380 hasConcept C150194340 @default.
• W1481210380 hasConcept C153911025 @default.
• W1481210380 hasConcept C2776985911 @default.
• W1481210380 hasConcept C2777426553 @default.
• W1481210380 hasConcept C2778609137 @default.
• W1481210380 hasConcept C2780876595 @default.
• W1481210380 hasConcept C529278444 @default.
• W1481210380 hasConcept C55493867 @default.
• W1481210380 hasConcept C55548728 @default.
• W1481210380 hasConcept C7821365 @default.
• W1481210380 hasConcept C86803240 @default.
• W1481210380 hasConcept C95444343 @default.
• W1481210380 hasConceptScore W1481210380C102230213 @default.
• W1481210380 hasConceptScore W1481210380C104317684 @default.
• W1481210380 hasConceptScore W1481210380C134018914 @default.
• W1481210380 hasConceptScore W1481210380C150194340 @default.
• W1481210380 hasConceptScore W1481210380C153911025 @default.
• W1481210380 hasConceptScore W1481210380C2776985911 @default.
• W1481210380 hasConceptScore W1481210380C2777426553 @default.
• W1481210380 hasConceptScore W1481210380C2778609137 @default.
• W1481210380 hasConceptScore W1481210380C2780876595 @default.
• W1481210380 hasConceptScore W1481210380C529278444 @default.
• W1481210380 hasConceptScore W1481210380C55493867 @default.
• W1481210380 hasConceptScore W1481210380C55548728 @default.
• W1481210380 hasConceptScore W1481210380C7821365 @default.
• W1481210380 hasConceptScore W1481210380C86803240 @default.
• W1481210380 hasConceptScore W1481210380C95444343 @default.
• W1481210380 hasLocation W14812103801 @default.
• W1481210380 hasOpenAccess W1481210380 @default.
• W1481210380 hasPrimaryLocation W14812103801 @default.
• W1481210380 hasRelatedWork W1583914179 @default.
• W1481210380 hasRelatedWork W1970780939 @default.
• W1481210380 hasRelatedWork W1971768862 @default.
• W1481210380 hasRelatedWork W1972262740 @default.
• W1481210380 hasRelatedWork W1978398040 @default.
• W1481210380 hasRelatedWork W1987493014 @default.
• W1481210380 hasRelatedWork W1996544632 @default.
• W1481210380 hasRelatedWork W1999786450 @default.
• W1481210380 hasRelatedWork W2001113932 @default.
• W1481210380 hasRelatedWork W2032345854 @default.
• W1481210380 hasRelatedWork W2045319760 @default.
• W1481210380 hasRelatedWork W2047833547 @default.
• W1481210380 hasRelatedWork W2070193133 @default.
• W1481210380 hasRelatedWork W2086192510 @default.
• W1481210380 hasRelatedWork W2128407755 @default.
• W1481210380 hasRelatedWork W2266699959 @default.
• W1481210380 hasRelatedWork W2299687031 @default.
• W1481210380 hasRelatedWork W2910120017 @default.
• W1481210380 hasRelatedWork W2975353528 @default.
• W1481210380 hasRelatedWork W3010815571 @default.
• W1481210380 isParatext "false" @default.
• W1481210380 isRetracted "false" @default.
• W1481210380 magId "1481210380" @default.
• W1481210380 workType "dissertation" @default.