Adam8-flox Mouse

ADAM8, also known as CD156a, is a member of the A Disintegrin And Metalloproteinase (ADAM) family of multifunctional, membrane-bound proteins. It has traditional sheddase functions, cleaving extracellular and membrane proteins, which is crucial for cell-cell communication. ADAM8 is involved in various pathways such as integrin signaling via its disintegrin domain binding to integrins like β1 integrin, activating focal adhesion kinase (FAK), extracellular regulated kinase (ERK1/2), and protein kinase B (AKT/PKB) signaling. It plays an important role in multiple biological processes, especially in inflammation and cancer [1,2,5,8].

In cancer, high ADAM8 expression is linked to invasiveness and poor patient outcomes in malignancies like breast, pancreatic, and brain cancer. It promotes cancer progression through proteolytic degradation of extracellular matrix components, cleavage of cell surface proteins, and non-proteolytic functions such as integrin signaling activation [1,5]. In asthma, its role is controversial, with some data suggesting it dampens airway inflammation while other studies question its role in leukocyte transmigration [2,4,6]. In myocardial infarction, macrophage-specific ADAM8 knockout mice show enhanced angiogenesis, suppressed inflammation, reduced cardiac fibrosis, and improved cardiac function, indicating that the ADAM8-ANXA2-mTOR-autophagy axis in macrophages regulates post-MI angiogenesis and inflammation [3]. In acute respiratory distress syndrome (ARDS), Adam8-/-mice have impaired neutrophil transmigration, and ADAM8 inhibition can fine-tune neutrophil responses [7]. In alcoholic liver fibrosis, ADAM8 promotes fibrosis through the MAPK signaling pathway [9].

In conclusion, ADAM8 is a key regulator in multiple disease conditions including cancer, asthma, cardiovascular diseases, and liver fibrosis. Gene knockout mouse models, such as macrophage-specific ADAM8 KO in myocardial infarction and Adam8-/-in ARDS, have been instrumental in revealing its role in specific biological processes. These models help understand how ADAM8 functions in disease development, providing potential therapeutic targets for these diseases.