TFR1 encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified.The membrane transferrin receptormediated endocytosis or internalization of the complex of transferrin bound iron and the transferrin receptor is the major route of cellular iron uptake. This efficient cellular uptake pathway has been exploited for the site-specific delivery not only of anticancer drugs and proteins, but also of therapeutic genes into proliferating malignant cells that overexpress the transferrin receptors. This is achieved either chemically by conjugation of transferrin with therapeutic drugs, proteins, or genetically by infusion of therapeutic peptides or proteins into the structure of transferrin. The resulting conjugates significantly improve the cytotoxicity and selectivity of the drugs. The coupling of DNA to transferrin via a polycation or liposome serves as a potential alternative to viral vector for gene therapy. Moreover, the OX26 monoclonal antibody against the rat transferrin receptor offers great promise in the delivery of therapeutic agents across the blood-brain barrier to the brain.
The exons 4-19 of mouse Tfr1 gene that encode the extracellular region were replaced by human TFR1 exons 4-19 in B-hTFR1 mice.
Protein expression analysis
Strain specific TFR1 expression analysis in homozygous B-hTFR1 mice by flow cytometry. Bone marrow was collected from wild-type C57BL/6 mice (+/+) and homozygous B-hTFR1 mice (H/H), and analyzed by flow cytometry with species-specific anti-TFR1 antibody. Mouse TFR1 was exclusively detectable in wild-type C57BL/6 mice. Human TFR1 was exclusively detectable in homozygous B-hTFR1 mice.