The tumor suppressor Fat1 is dispensable for normal murine hematopoiesis

Abstract

Abstract Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.