Nomenclature: C57BL/6NTac-Tfrc^{tm2618.1(TFRC)Tac}

• Homozygous for transferrin receptor (TFRC) with humanized extracellular domain
• TFRC encodes transferrin receptor-1 (TfR1), a cell-surface receptor required for import of iron from transferrin into cells by receptor-mediated endocytosis
• TfR1 transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders
• This model may be useful for evaluating the efficacy of receptor-mediated transcytosis-based therapeutics targeting the CNS, including neuroinflammation and neurodegenerative diseases. 
• This model may be useful for the study of iron metabolism, anemia, and neurodegenerative disorders.
• TfR1 is expressed in numerous types of cancer cells, targeting TfR1 has been demonstrated to effectively suppress tumor growth and metastasis
• hTFRC mice have normal RBC and hemoglobin levels with signs of very mild macrocytic anemia in males

Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation. 

Origin

The hTFRC mouse was developed in partnership with Boehringer Ingelheim GmbH. The model was created by homologous recombination to generate a constitutive humanization of the full extracellular domain (aa 89-760) of the transferrin receptor (Tfrc) in the C57BL/6NTac background. The targeting vector was generated using mouse (RPCIB-731) and human (RPCIB-753) BAC clones and transfected into B6NTac ESCs. Homologous recombinant clones were isolated using double positive selection flanked by FRT (NeoR) and F3 (PuroR) sites inserted into the human intron 4 and downstream of the mouse 3’ untranslated region (UTR). The humanized allele was obtained after Flp-mediated removal of these selection markers. The resulting chimeric mouse-human TFRC gene (protein is a fusion between mouse cytoplasmic plus transmembrane and human extracellular domains) expresses under the control of the endogenous mouse Tfrc promoter. Residual recombination sites are located in non-conserved regions of the genome. Taconic received homozygous stock in 2024 and backcrossed to B6NTac. The colony is maintained through the mating of homozygotes.