Grb2-flox Mouse

Grb2, also known as Growth factor receptor-bound protein 2, is a 25-kDa adaptor protein. It contains a central Src homology type 2 (SH2) domain flanked by two Src homology type 3 (SH3) domains. Grb2 is pivotal in multiple cellular functions, acting as an intermediate in signal transduction pathways. It links cell-surface activated receptors to downstream targets, regulating pathways such as the activation of RAS and its downstream kinases like ERK1,2, as well as being involved in processes like cell growth, proliferation, and metabolism [3,4,5].

In a syngeneic mouse metastatic ovarian cancer model, GRB2 depletion in combination with PARP inhibitor treatment reduced tumor burden and increased survival. This indicates that GRB2 plays a role in genomic stability at stalled replication forks, and its depletion can trigger innate immunity against cancer through the release of DNA fragments from stalled forks, activating the cGAS-STING pathway [1]. In another study, in ovo studies in a CAM model showed that GRB2 knockdown, as well as overexpression of GRB2 loss-of-function mutants, compromised tumor growth, suggesting its role in tumorigenesis through regulating autophagy [2]. In systemic sclerosis, GRB2 was highly expressed in endothelial cells of SSc skin, and inhibiting GRB2 could effectively attenuate bleomycin-induced skin fibrosis and endothelial cell apoptosis in mouse models [6].

In conclusion, Grb2 is essential for multiple cellular functions and is involved in key signaling pathways. Through model-based research, especially in mouse models, its role in cancer, autophagy, and systemic sclerosis has been revealed. These findings suggest that Grb2 could be a potential therapeutic target for these diseases.