Matches in SemOpenAlex for { <https://semopenalex.org/work/W2103666098> ?p ?o ?g. }
Showing items 1 to 92 of
92
with 100 items per page.
- W2103666098 endingPage "993" @default.
- W2103666098 startingPage "984" @default.
- W2103666098 abstract "Treatment of many inherited liver enzyme deficiencies requires the removal of toxic intermediate metabolites from the blood of affected individuals. We propose that circulating toxins can be adequately cleared and disease phenotype influenced by enzyme expressed in tissues other than the liver, such as bone marrow. Our specific hypothesis was that phenylalanine hydroxylase (PAH) expressed in bone marrow would lower blood phenylalanine levels in hyperphenylalaninemic Pah(enu2) mice, a model of human phenylketonuria (PKU).Germline-modified marrow PAH-expressing mice were developed using a transgene that contained the mouse liver PAH cDNA under the transcriptional control of a human beta-globin promoter. Marrow PAH-expressing mice were bred to Pah(enu2) mice to generate progeny that lacked liver PAH activity but expressed PAH in bone marrow.Marrow PAH expression did not affect the health, function, or reproductive capacity of transgenic animals. Hyperphenylalaninemia persisted in transgenic Pah(enu2) homozygous mice despite PAH activity in marrow lysates, and was not altered following supplementation with tetrahydrobiopterin (BH(4)), a required cofactor for PAH. PAH activity measured in intact marrow cells was significantly lower than in marrow lysates; no such difference was measured in isolated hepatocytes vs. liver homogenate.Marrow PAH expression did not correct hyperphenylalaninemia in Pah(enu2) mice. Phenylalanine clearance may have been limited by the natural perfusion rate of the marrow compartment, by insufficient PAH expression in marrow, or by other cellular factors affecting phenylalanine metabolism in intact marrow cells. Differences in PAH activity measured in intact marrow cells vs. cell lysates suggest that hepatocytes and PAH-expressing marrow cells are fundamentally different in their ability to metabolize phenylalanine. The efficacy of bone-marrow-directed gene therapy as a metabolic sink in the treatment of phenylketonuria may be limited, although further experiments with greater marrow PAH expression levels will be necessary to definitively prove this conclusion." @default.
- W2103666098 created "2016-06-24" @default.
- W2103666098 creator A5002194433 @default.
- W2103666098 creator A5021636969 @default.
- W2103666098 creator A5057312365 @default.
- W2103666098 creator A5060947834 @default.
- W2103666098 creator A5072550388 @default.
- W2103666098 date "2003-01-01" @default.
- W2103666098 modified "2023-10-12" @default.
- W2103666098 title "Expression of phenylalanine hydroxylase (PAH) in erythrogenic bone marrow does not correct hyperphenylalaninemia inPahenu2 mice" @default.
- W2103666098 cites W1533407122 @default.
- W2103666098 cites W1968458490 @default.
- W2103666098 cites W1982581996 @default.
- W2103666098 cites W1994249563 @default.
- W2103666098 cites W1995612506 @default.
- W2103666098 cites W203149856 @default.
- W2103666098 cites W2058690697 @default.
- W2103666098 cites W2065838703 @default.
- W2103666098 cites W2074488303 @default.
- W2103666098 cites W2079149764 @default.
- W2103666098 cites W2090122012 @default.
- W2103666098 cites W2097794242 @default.
- W2103666098 cites W2163057250 @default.
- W2103666098 cites W2169845675 @default.
- W2103666098 cites W2315750634 @default.
- W2103666098 cites W2404242464 @default.
- W2103666098 cites W59490061 @default.
- W2103666098 doi "https://doi.org/10.1002/jgm.432" @default.
- W2103666098 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2694059" @default.
- W2103666098 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14601136" @default.
- W2103666098 hasPublicationYear "2003" @default.
- W2103666098 type Work @default.
- W2103666098 sameAs 2103666098 @default.
- W2103666098 citedByCount "12" @default.
- W2103666098 countsByYear W21036660982013 @default.
- W2103666098 countsByYear W21036660982016 @default.
- W2103666098 countsByYear W21036660982017 @default.
- W2103666098 crossrefType "journal-article" @default.
- W2103666098 hasAuthorship W2103666098A5002194433 @default.
- W2103666098 hasAuthorship W2103666098A5021636969 @default.
- W2103666098 hasAuthorship W2103666098A5057312365 @default.
- W2103666098 hasAuthorship W2103666098A5060947834 @default.
- W2103666098 hasAuthorship W2103666098A5072550388 @default.
- W2103666098 hasBestOaLocation W21036660982 @default.
- W2103666098 hasConcept C126322002 @default.
- W2103666098 hasConcept C134018914 @default.
- W2103666098 hasConcept C185592680 @default.
- W2103666098 hasConcept C203014093 @default.
- W2103666098 hasConcept C207009774 @default.
- W2103666098 hasConcept C2777431362 @default.
- W2103666098 hasConcept C2780007613 @default.
- W2103666098 hasConcept C2780968477 @default.
- W2103666098 hasConcept C515207424 @default.
- W2103666098 hasConcept C55493867 @default.
- W2103666098 hasConcept C71924100 @default.
- W2103666098 hasConcept C86803240 @default.
- W2103666098 hasConceptScore W2103666098C126322002 @default.
- W2103666098 hasConceptScore W2103666098C134018914 @default.
- W2103666098 hasConceptScore W2103666098C185592680 @default.
- W2103666098 hasConceptScore W2103666098C203014093 @default.
- W2103666098 hasConceptScore W2103666098C207009774 @default.
- W2103666098 hasConceptScore W2103666098C2777431362 @default.
- W2103666098 hasConceptScore W2103666098C2780007613 @default.
- W2103666098 hasConceptScore W2103666098C2780968477 @default.
- W2103666098 hasConceptScore W2103666098C515207424 @default.
- W2103666098 hasConceptScore W2103666098C55493867 @default.
- W2103666098 hasConceptScore W2103666098C71924100 @default.
- W2103666098 hasConceptScore W2103666098C86803240 @default.
- W2103666098 hasIssue "11" @default.
- W2103666098 hasLocation W21036660981 @default.
- W2103666098 hasLocation W21036660982 @default.
- W2103666098 hasLocation W21036660983 @default.
- W2103666098 hasLocation W21036660984 @default.
- W2103666098 hasOpenAccess W2103666098 @default.
- W2103666098 hasPrimaryLocation W21036660981 @default.
- W2103666098 hasRelatedWork W1964505813 @default.
- W2103666098 hasRelatedWork W1973203264 @default.
- W2103666098 hasRelatedWork W2089659821 @default.
- W2103666098 hasRelatedWork W2098425369 @default.
- W2103666098 hasRelatedWork W2099514779 @default.
- W2103666098 hasRelatedWork W2136967346 @default.
- W2103666098 hasRelatedWork W2368728617 @default.
- W2103666098 hasRelatedWork W2388084951 @default.
- W2103666098 hasRelatedWork W2413105122 @default.
- W2103666098 hasRelatedWork W3146185591 @default.
- W2103666098 hasVolume "5" @default.
- W2103666098 isParatext "false" @default.
- W2103666098 isRetracted "false" @default.
- W2103666098 magId "2103666098" @default.
- W2103666098 workType "article" @default.