Serpina1 (a-e) KO Mouse

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 (Glu342Lys), lead to alpha-1 antitrypsin deficiency (AATD), resulting in emphysema and chronic obstructive pulmonary disease (COPD) due to uncontrolled protease activity. Additionally, misfolded AAT accumulation in hepatocytes may cause cirrhosis or hepatocellular carcinoma ^[1-3]. The affected tissues primarily include the liver and lungs, with the former being damaged by protein aggregation and the latter by tissue destruction. This highlights AAT's systemic role in protease regulation and disease pathology.

Serpina1(a-e) KO mice are gene knockout (KO) models created by gene editing technology to knock out the protein-coding sequences of the Serpina1(a-e) genes (homologous to the human SERPINA1 gene) in mice. Preliminary data indicate almost no expression of the Serpina1 gene in the liver of these mice, with no significant pulmonary abnormalities observed at 8 weeks of age. Serpina1(a-e) KO mice can be used to study the pathogenic mechanisms of emphysema and chronic obstructive pulmonary disease (COPD), cirrhosis, and hepatocellular carcinoma, as well as to develop related therapeutic approaches.