Flot2-flox Mouse

Flot2, also known as flotillin-2, is a lipid raft scaffold protein. It is thought to be involved in various biological processes such as endocytosis, neural differentiation, and may be related to multiple signaling pathways. It has shown importance in maintaining normal cellular functions and its dysregulation is associated with several diseases [3].

In sepsis, Flot2 deficiency in B cells, as shown by Flot2 knockout (Flot2-/-) mice, leads to up-regulation of effector B cell cytokines like Il6, Il1b and Cxcl10, aggravating sepsis with increased lung injury and shortened survival time. This indicates Flot2 is a controller of B cells and its deficiency amplifies inflammation in sepsis [1].

In proteinuric kidney disease, podocyte-specific Flot2 deletion worsens albuminuria, podocyte injury and glomerular pathology in mouse models, while overexpression prevents these, suggesting Flot2 stabilizes the podocin-nephrin complex in lipid rafts of podocytes [2].

In conclusion, Flot2 plays essential roles in maintaining normal B-cell-mediated immune responses and podocyte function. The Flot2 KO/CKO mouse models have been crucial in revealing its roles in sepsis and proteinuric kidney disease, providing insights into the pathogenesis of these diseases and potential therapeutic targets.