Characterizing the biological role of lactoferrin in early life using a lactoferrin receptor knockout mouse model (38.7)

Abstract

The iron‐binding glycoprotein lactoferrin (Lf) is highly abundant in human milk. Lf is hypothesized to exert various effector functions within the GI tract of the infant including maturation of the intestinal epithelium and immune system. A lactoferrin receptor (LfR) has been isolated from human fetal and mammalian small intestine (e.g., mouse and pig), and has been shown to facilitate cellular uptake and intracellular trafficking of Lf. Despite strong evidence indicating that the LfR orchestrates multiple biological activities ascribed to Lf, there is currently no in vivo evidence attributing the regulatory mechanisms and tissue‐specific functions of Lf to the LfR. Our laboratory has developed the first LfR knockout mouse model to investigate the physiological role of Lf and the LfR during early life. Global gene and protein ablation was confirmed by PCR and Western blot analysis of multiple tissues. Protein expression analysis showed the LfR is highly expressed within mucosal tissues (e.g., small intestine and lungs) and at site‐specific regions of tissues directing global metabolism (e.g., liver and kidneys), suggesting that the LfR likely serves a role in host defense. The intestinal mucosa of the infant is a primary site for maternally derived protective factors. The LfR may exert intrinsic activity as a component of the mucosal immune milieu and also direct the activities of milk‐derived Lf.