Functional characterization of the mouse Serpina1 paralog DOM-7

• Published in: Biological chemistry Vol. 399; no. 6; pp. 577 - 582
• Main Authors: Jülicher, Karen, Wähner, Annabell, Haase, Kerstin, Barbour, Karen W., Berger, Franklin G., Wiehlmann, Lutz, Davenport, Colin, Schuster-Gossler, Karin, Stitz, Jörn, Cantz, Tobias, Eggenschwiler, Reto
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 24.05.2018; Walter de Gruyter GmbH
• Subjects: alpha 1-Antitrypsin - metabolism; Animal models; Animals; antitrypsin deficiency; Chymotrypsin; Complexity; CRISPR; DOM-7; Elastase; Genomes; Leukocytes (neutrophilic); Loci; Mice; Mice, Inbred BALB C; neutrophil elastase; Proteinase; Serpina; antitrypsin deficiency; Serpina; chymotrypsin; neutrophil elastase; DOM-7
• ISSN: 1431-6730; 1437-4315
• DOI: 10.1515/hsz-2018-0154

The generation of authentic mouse-models for human α1-antitrypsin (A1AT)-deficiency is difficult due to the high complexity of the mouse gene . Depending on the exact mouse strain, three to five paralogs are expressed, with different proteinase inhibitory properties. Nowadays with CRISPR-technology, genome editing of complex genomic loci is feasible and could be employed for the generation of A1AT-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 neutrophil elastase (ELANE) and chymotrypsin, and therefore needs to be considered when aiming at the generation of A1AT-deficient models.