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dc.contributor.authorEggenschwiler, Reto
dc.contributor.authorPatronov, Atanas
dc.contributor.authorHegermann, Jan
dc.contributor.authorFráguas-Eggenschwiler, Mariane
dc.contributor.authorWu, Guangming
dc.contributor.authorCortnumme, Leon
dc.contributor.authorOchs, Matthias
dc.contributor.authorAntes, Iris
dc.contributor.authorCantz, Tobias
dc.date.accessioned2019-07-09T11:49:13Z
dc.date.available2019-07-09T11:49:13Z
dc.date.issued2019-05-16
dc.identifier.citationSci Rep. 2019 May 16;9(1):7486. doi: 10.1038/s41598-019-44043-3.en_US
dc.identifier.issn2045-2322
dc.identifier.pmid31097772
dc.identifier.doi10.1038/s41598-019-44043-3
dc.identifier.urihttp://hdl.handle.net/10033/621854
dc.description.abstractCertain point-mutations in the human SERPINA1-gene can cause severe α1-antitrypsin-deficiency (A1AT-D). Affected individuals can suffer from loss-of-function lung-disease and from gain-of-function liver-disease phenotypes. However, age of onset and severity of clinical appearance is heterogeneous amongst carriers, suggesting involvement of additional genetic and environmental factors. The generation of authentic A1AT-D mouse-models has been hampered by the complexity of the mouse Serpina1-gene locus and a model with concurrent lung and liver-disease is still missing. Here, we investigate point-mutations in the mouse Serpina1a antitrypsin-orthologue, which are homolog-equivalent to ones known to cause severe A1AT-D in human. We combine in silico and in vitro methods and we find that analyzed mutations do introduce potential disease-causing properties into Serpina1a. Finally, we show that introduction of the King’s-mutation causes inactivation of neutrophil elastase inhibitory-function in both, mouse and human antitrypsin, while the mouse Z-mutant retains activity. This work paves the path to generation of better A1AT-D mouse-models.en_US
dc.publisherSpringer-Natureen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleA combined in silico and in vitro study on mouse Serpina1a antitrypsin-deficiency mutants.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalScientific reportsen_US
refterms.dateFOA2019-07-09T11:49:13Z
dc.source.journaltitleScientific reports


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Attribution-NonCommercial-ShareAlike 4.0 International
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