Pfkfb2-flox Mouse

Pfkfb2, also known as 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2, is a key regulator of the glycolytic enzyme. It participates in regulating glycolysis, a metabolic pathway crucial for energy production and biosynthesis in cells. Glycolysis is associated with various biological processes such as cell proliferation, differentiation, and the body's response to inflammation [1,2,3,4,5,6,7,8].

In mice, transplantation of activation-defective Pfkfb2 bone marrow leads to impaired thymic efferocytosis, increased thymic necrosis, and lower expression of efferocytosis receptors MerTK and LRP1 on thymic macrophages, indicating its role in the process of macrophages clearing apoptotic cells [1]. In colorectal cancer, knockdown of Pfkfb2 in alkaline culture medium enhances the abilities of migration, invasion, spheroidizing ability, proliferation, and colony formation of CRC cells, while overexpression in acidic culture medium has the opposite effect. This shows that Pfkfb2 can inhibit the metastasis and malignant progression of CRC cells by suppressing the epithelial-mesenchymal transition (EMT) and glycolysis [2]. In myocardial ischemia/reperfusion injury, overexpression of Pfkfb2 in mice protects the heart against ferroptosis through activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway [3]. Loss of cardiac Pfkfb2 in a cardiomyocyte-specific knockout (cKO) mouse model results in metabolic, functional, and electrophysiological remodeling in the heart, with cKO mice showing increased glycolytic enzyme abundance, decreased mitochondrial abundance, impaired systolic function, and electrophysiological alterations [6].

In conclusion, Pfkfb2 plays a vital role in multiple biological processes mainly through its regulation of glycolysis. Mouse models, especially KO/CKO models, have been instrumental in revealing its functions in diseases such as chronic inflammatory diseases, colorectal cancer, myocardial ischemia/reperfusion injury, and cardiac-related pathologies. These findings suggest that Pfkfb2 could be a potential therapeutic target for these diseases [1,2,3,6].