Functional characterization of the mouse Serpina1 paralog DOM-7
-
Karen Jülicher
und
Reto Eggenschwiler
Abstract
The generation of authentic mouse-models for human α1-antitrypsin (A1AT)-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. 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.
Acknowledgments
This work was supported by the German Research Foundation through the excellence cluster REBIRTH (DFG EXC 62/3) and the collaborative research center ‘Optimization of Conventional and Innovative Transplants’ (CRC 738). R.E. received support from Hannover Medical School via the ‘Hochschulinterne Leistungsförderung’ (HiLF) program.
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Supplemental Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0154).
©2018 Walter de Gruyter GmbH, Berlin/Boston
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Artikel in diesem Heft
- Frontmatter
- Reviews
- Hodgkin lymphoma cell lines: to separate the wheat from the chaff
- The AGO proteins: an overview
- Research Articles/Short Communications
- Protein Structure and Function
- Structural changes at the myrtenol backbone reverse its positive allosteric potential into inhibitory GABAA receptor modulation
- The two major glucokinase isoforms show conserved functionality in β-cells despite different subcellular distribution
- Functional characterization of the mouse Serpina1 paralog DOM-7
- Cell Biology and Signaling
- CD45RO regulates the HIV-1 gp120-mediated apoptosis of T cells by activating Lck
- Silencing of MED27 inhibits adrenal cortical carcinogenesis by targeting the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition process
- HDAC1 knockdown inhibits invasion and induces apoptosis in non-small cell lung cancer cells
- Hepatitis B virus X protein promotes proliferation of hepatocellular carcinoma cells by upregulating miR-181b by targeting ING5
