Bag2-flox Mouse

Bag2, also known as BCL2-associated athanogene 2, is a co-chaperone. It interacts with the ATPase domain of heat shock protein 70 (dHsp70) via its BAG domain and is involved in multiple cellular processes like apoptosis, autophagy, protein folding, and homeostasis. It is associated with various pathways and plays a significant role in the pathogenesis of multiple diseases, including cancers and neurodegenerative diseases [2,3]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable for studying its function.

In a DIC model using C57BL/6 mice, Bag2 expression was significantly reduced after doxorubicin (DOX) treatment. Bag2 knockdown led to apoptosis, mitochondrial dysfunction, and impaired mitophagy, similar to DOX administration. Conversely, Bag2 overexpression protected against these phenotypes. Mechanistically, Bag2 maintained mitophagy activation by binding to Pink1 and protecting it from proteasome-dependent degradation, protecting against myocardial lesions [1]. In breast cancer, high BAG2 expression in patient tissues was associated with a worse prognosis. BAG2 exacerbated mutant p53 aggregate formation, inhibiting the mitochondrial apoptosis pathway and leading to chemoresistance. Silencing BAG2 increased chemotherapy sensitivity [4].

In conclusion, Bag2 is crucial in maintaining cellular homeostasis, especially in processes like mitophagy. Studies using KO/CKO mouse models have revealed its role in diseases such as doxorubicin-induced cardiotoxicity and breast cancer chemoresistance. Understanding Bag2's functions provides potential therapeutic targets for these and other related diseases.