TG-hSERPINA1*E366K Mouse
Product Name
TG-hSERPINA1*E366K Mouse
Product ID
I001123
Strain Name
C57BL/6JCya-Tg(hSERPINA1*E366K)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “TG-hSERPINA1*E366K Mouse (Catalog I001123) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
SERPINA1
Gene Alias
PI, A1A, AAT, PI1, A1AT, nNIF, PRO2275, alpha1AT
NCBI ID
Chromosome
Chr 14 (Human)
MGI ID
Datasheet
Strain Description
The SERPINA1 gene encodes alpha-1 antitrypsin (AAT), a serine protease inhibitor primarily synthesized and secreted by hepatocytes in the liver, with additional expression in immune cells such as macrophages. AAT's main function is to inhibit neutrophil-derived proteases (e.g., elastase) to protect lung tissue from enzymatic degradation. This glycoprotein is crucial for maintaining lung tissue elasticity and regulating inflammatory responses. Mutations in the Serpina1 gene, particularly the Z variant (such as the most common mutation p.E366K), can cause alpha-1 antitrypsin deficiency (AATD), which in turn leads to emphysema and chronic obstructive pulmonary disease (COPD). The pathological mechanism of these diseases stems from dysregulated protease activity. Additionally, the intracellular accumulation of misfolded AAT in hepatocytes may also induce cirrhosis or hepatocellular carcinoma [1-3]. Individuals carrying the ZZ genotype face the highest risk of developing pulmonary and hepatic disease manifestations: in the liver, protein aggregation causes cellular damage; in the lungs, tissue destruction triggers disease [4]. This highlights AAT's systemic role in protease regulation and disease pathology.
The TG-hSERPINA1*E366K mouse is generated by integrating the Human SERPINA1 Genomic DNA (the region from ~5kb upstream of exon 1 to ~3kb downstream of exon 5) into the mouse genome via transgenesis (TG) technology. A p.E366K (GAG to AAG) point mutation is introduced into exon 5 of this integrated human SERPINA1 sequence. This model can be used to study diseases such as alpha-1 antitrypsin deficiency (AATD), emphysema, chronic obstructive pulmonary disease (COPD), cirrhosis, and hepatocellular carcinoma, as well as to develop relevant therapeutic strategies.
Reference
Stoller, J. K., & Aboussouan, L. S. (2012). Alpha1-antitrypsin deficiency. The Lancet, 365(9478), 2225-2236.
Greene CM, McElvaney NG. Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response. World J Gastrointest Pharmacol Ther. 2010 Oct 6;1(5):94-101.
Lomas DA, Mahadeva R. Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy. J Clin Invest. 2002 Dec;110(11):1585-90.
Pac LJ, Cheeney G, Westerhoff M, Konnick EQ, Greene DN, Lockwood CM. Real-Time PCR to Detect α-1 Antitrypsin S and Z Alleles in Formalin-Fixed Paraffin-Embedded Tissue. J Appl Lab Med. 2018 Jul 1;3(1):18-25.
Strain Strategy
The Human SERPINA1 Genomic DNA (the region from upstream of exon 1 to downstream of exon 5) was integrated into the mouse genome via transgenesis (TG) technology. The p.E366K (GAG to AAG) point mutation was introduced into exon 5.
Figure 1. Gene editing strategy of TG-hSERPINA1*E366K mice.
Application Area
Research on alpha-1 antitrypsin deficiency (AATD);
Research on emphysema and chronic obstructive pulmonary disease (COPD);
Research on cirrhosis or hepatocellular carcinoma.
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