Background：

• TFR1 is a membrane protein essential for iron transport and metabolism, expressed across diverse human tissues. It is markedly upregulated in many cancers, where targeting TFR1 can suppress tumor growth and metastasis. Beyond oncology, TFR1 is also implicated in anemia, neurodegenerative disorders, and other conditions.
• Because TFR1 is highly expressed on brain endothelial cells, it can be leveraged for receptor-mediated transcytosis (RMT), enabling efficient transport of large molecules across the BBB and making it an attractive target for CNS drug delivery.

Targeting strategy:

• In B-hTFR1 rats plus, the genomic sequence of the rat Tfr1 gene encoding the extracellular domain is replaced by its human TFR1 counterpart.

Application:

• Evaluate the pharmacodynamics and safety of anti-tumor and neurodegenerative disease treatments.
• Access drug penetration across the blood–brain barrier (BBB) and muscle.

Gene targeting strategy for B-hTFR1 rats plus. The exons 4-19 of rat Tfr1 gene that encode extracellular domain are replaced by human counterparts in B-hTFR1 rats plus. The genomic region of rat Tfr1 gene that encodes cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the rat gene are also retained. The chimeric TFR1 expression is driven by endogenous rat Tfr1 promoter, while rat Tfr1 gene transcription and translation will be disrupted.

• Rat TFR1 was detectable in wild-type SD rats. Human TFR1 was exclusively detectable in heterozygous B-hTFR1 rats plus.

Strain specific TFR1 expression analysis in heterozygous B-hTFR1 rats plus by flow cytometry. Bone marrow was collected from wild-type SD rats (+/+) and heterozygous B-hTFR1 rats plus (H/+) (male, 6-week-old). Protein expression was analyzed with anti-rat TFR1 antibody (Biolegend, 204410) and anti-human TFR1 antibody (Biolegend, 334108) by flow cytometry in bone marrow erythrocytes.