Fgb-flox Mouse

Fgb, which encodes the Bβ chain of fibrinogen, is a crucial gene. Fibrinogen, a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), plays an essential role in hemostasis. The conversion of fibrinogen to insoluble polymer fibrin provides structural stability, strength, and adhesive surfaces for blood clots. It also has antithrombotic properties after fibrin clot formation. Besides hemostasis and thrombosis, fibrinogen and fibrin are involved in multiple biological processes such as fibrinolysis, matrix physiology, wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis [1].

Mutations in Fgb can lead to congenital fibrinogen deficiencies, which are rare bleeding disorders with extensive genetic heterogeneity. These mutations can cause variable clinical manifestations, ranging from asymptomatic conditions to life-threatening bleeds or thromboembolic events. For example, a novel homozygous missense mutation in FGB exon 5, p.Cys241Tyr, named "Fibrinogen Krakow V", was found in a male patient with congenital afibrinogenemia who presented with recurrent intracranial hemorrhages [6]. In addition, Fgb expression is abnormally regulated in several cancers. In renal cell carcinoma (RCC), SIRT1 downregulates FGB expression to inhibit tumorigenesis by destabilizing STAT3 [2]. In breast cancer, FGB is more highly expressed, and miR-877-5p can inhibit epithelial-mesenchymal transformation, cell proliferation, and invasion of breast cancer cells via downregulating FGB [4]. In lung adenocarcinoma (LUAD), circ_16601 promotes LUAD progression through the miR-5580-5p/FGB axis by facilitating Hippo pathway signaling [5]. Also, FGB and FGG derived from plasma exosomes might be potential biomarkers to distinguish benign from malignant pulmonary nodules [3].

In conclusion, Fgb is essential for the normal function of fibrinogen in hemostasis and a wide range of biological processes. Its abnormal regulation is associated with various bleeding and thrombotic disorders, as well as cancers. The study of Fgb-related mutations and its expression regulation in different disease models helps to understand the underlying molecular mechanisms, providing potential targets for disease diagnosis, prognosis, and treatment.