ena-STUDY-MHH-09-02-2018-13:24:23:957-1180
Functional characterization of mouse Serpina1 DOM-7
The generation of authentic mouse-models for human a1-antitrypsin-deficiency is difficult due to the high complexity of the mouse Serpina1 gene-locus. Depending on the exact mouse strain, three to five paralogs are expressed, with different proteinase inhibitory properties. With modern CRISPR-technology, genome editing of complex genomic loci is feasible and could be employed for generation of a1-antitrypsin-deficiency mouse-models. In preparation of a CRISPR/Cas9-based genome-engineering approach we identified cDNA clones with a functional CDS for the Serpina1-paralog DOM-7. Here, we show that DOM-7 functionally inhibits Elane and chymotrypsin, and therefore needs to be considered when aiming at the generation of a1-antitrypsin-deficiency models.
The generation of authentic mouse-models for human a1-antitrypsin-deficiency is difficult due to the high complexity of the mouse Serpina1 gene-locus. Depending on the exact mouse strain, three to five paralogs are expressed, with different proteinase inhibitory properties. With modern CRISPR-technology, genome editing of complex genomic loci is feasible and could be employed for generation of a1-antitrypsin-deficiency mouse-models. In preparation of a CRISPR/Cas9-based genome-engineering approach we identified cDNA clones with a functional CDS for the Serpina1-paralog DOM-7. Here, we show that DOM-7 functionally inhibits Elane and chymotrypsin, and therefore needs to be considered when aiming at the generation of a1-antitrypsin-deficiency models.