Fundc2-flox Mouse

FUNDC2, also known as HCBP6, is a highly conserved and ubiquitously expressed mitochondrial outer membrane protein. It plays crucial roles in multiple biological processes. It is involved in pathways related to ferroptosis, mitochondrial dynamics, platelet activation, and cancer-related signaling pathways [1,2,3,4]. Genetic models, especially KO mouse models, have been instrumental in studying its functions.

In KO mouse models, knockout of FUNDC2 protected mice from doxorubicin-induced cardiac injury by preventing ferroptosis, as FUNDC2 interacts with SLC25A11 to regulate mitoGSH levels [1]. In liver tumorigenesis, knockdown of FUNDC2 in mice inhibited liver tumor growth by promoting mitochondrial elongation as it usually inhibits MFN1-mediated mitochondrial fusion [2]. FUNDC2-knockout mice also displayed deficiency in haemostasis and thrombosis, as FUNDC2 positively regulates platelet functions via AKT/GSK-3β/cGMP signalling pathways [3]. In TNBC, FUNDC2 silencing in TNBC cells significantly reduced cell proliferation, migration, and invasion, and suppressed tumor growth in subcutaneous tumor xenografts in mice [4].

In conclusion, FUNDC2 is a key mitochondrial protein involved in ferroptosis, mitochondrial dynamics, platelet activation, and cancer progression. Studies using KO mouse models have revealed its roles in doxorubicin-induced cardiomyopathy, liver tumorigenesis, platelet-related diseases, and triple-negative breast cancer, providing potential therapeutic targets for these diseases.