Flt3l-KO Mouse

Flt3l, also known as FMS-related tyrosine kinase 3 ligand and encoded by FLT3LG, is a hematopoietic factor. It acts on Flt3-expressing multipotent progenitors and common lymphoid progenitors. The Flt3/Flt3L axis is crucial for the generation of conventional DCs (cDCs) and plasmacytoid DCs (pDCs), and Flt3 signaling through PI3K and mTOR may affect mature DC function [2].

In mice, Flt3l is essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) [1]. In humans, three individuals homozygous for a loss-of-function FLT3LG variant had hypoplastic bone marrow, low levels of hematopoietic progenitors, and low counts of B cells, monocytes, and DCs in the blood. Unlike in mice, human Flt3L is required for monocyte development but not NK cell development [1]. Maternal low-fiber diet in mice reduced neonatal intestinal epithelial cell secretion of Flt3L, impairing pDC hematopoiesis and increasing LRI severity in offspring [3].

In conclusion, Flt3l is vital for the development of multiple hematopoietic lineages in both mice and humans, with some differences between species. Mouse models with loss-of-function of Flt3l have revealed its role in immune cell development and responses, such as in relation to respiratory infections, which may have implications for understanding and treating related human diseases.