Bag3-flox Mouse

Bag3, also known as B-cell lymphoma 2-associated athanogene 3, is a co-chaperone protein that plays a crucial role in multiple biological processes. It is involved in pathways such as autophagy, apoptosis, and proteostasis [3,4,5]. Bag3 is essential for maintaining protein homeostasis in stressed cells, promoting chaperone activity, sequestering misfolded proteins, and initiating autophagic disposal [5]. It has been found to be ubiquitously expressed, with prominent expression in cardiac and skeletal muscle, the brain, and many cancers [4].

In mouse models, global post-natal deletion of Bmal1 in tauopathy or alpha-synucleinopathy models led to an unexpected suppression of tau and alpha-synuclein aggregation. Astrocyte-specific Bmal1 deletion was sufficient to prevent these pathologies in vivo, which was accompanied by astrocyte activation and increased Bag3 expression. Astrocyte Bag3 overexpression mitigated alpha-synuclein spreading in vivo, suggesting that Bag3 has a protective role against tau and alpha-synuclein pathologies [1]. Also, in ischemic stroke models, BAG3 overexpression activated autophagy and inhibited apoptosis, alleviating ischemic stroke injury [2].

In conclusion, Bag3 is a multi-functional protein essential for proteostasis, autophagy, and apoptosis regulation. Mouse models, especially those with gene deletions, have revealed its significance in neurodegenerative diseases like tauopathy and alpha-synucleinopathy, as well as in ischemic stroke. Understanding Bag3's function provides potential therapeutic insights for these disease areas.