Fn1-flox Mouse

Fn1, short for fibronectin 1, is a glycoprotein present throughout the extracellular matrix. It plays crucial roles in cell adhesion, migration, and differentiation, and is involved in multiple biological processes such as embryonic development, tissue repair, and angiogenesis. It is associated with pathways like autophagy-lysosome, integrin-mediated signaling, and S1PR1/AKT pathway [1,2,5]. Genetic models, especially knockout (KO) mouse models, are valuable for studying Fn1's functions.

In head-and-neck squamous cell carcinoma (HNSCC), autophagy promotes the degradation of FN1 via the p62/SQSTM1-dependent autophagy-lysosome pathway, and high FN1 expression correlates with poorer prognosis [1]. In Alzheimer's disease, a rare genetic variation in FN1 protects against APOEε4-mediated pathology, and loss-of-function (LOF) mutations in the zebrafish ortholog fn1b reduce gliosis and enhance gliovascular remodeling [3]. In calcified chondroid mesenchymal neoplasms, FN1-receptor tyrosine kinase gene fusions are detected, including novel fusions like FN1-MERTK, FN1-NTRK1, and FN1-TEK [4]. In gastric cancer, high FN1 expression is related to cancer progression and is a prognostic biomarker associated with immune infiltrates, especially macrophage infiltration [6,7]. In the development of the third pharyngeal pouch, loss of Fn1 in neural crest cells (NCCs) leads to abnormal development of thymus/parathyroid derivatives [8].

In summary, Fn1 is essential for normal development and is involved in disease processes such as cancer, Alzheimer's disease. The study of Fn1 using KO models in various systems has provided insights into its role in these biological and disease-related processes, potentially guiding the development of new therapeutic strategies for these diseases.