A combined in silico and in vitro study on mouse Serpina1a antitrypsin-deficiency mutants.

ABSTRACT: Certain 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 analyze

SUBMITTER: Eggenschwiler R 

PROVIDER: S-EPMC6522476 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature