The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[1]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[2]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis ^[1]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients ^[3]. As a target for antibody-mediated cancer therapy, TFR1 can be leveraged through two approaches: one involves the use of antibodies conjugated to anti-cancer drugs, which are indirectly internalized via receptor-mediated endocytosis; the other employs antibodies that directly disrupt receptor function or induce Fc effector functions such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Various clinical drugs targeting TFR1 are currently under development, including antisense oligonucleotides (ASOs), antibody-drug conjugates (ADCs), and antibody-oligonucleotide conjugates, applicable to diseases such as cancer, anemia, and neurodegenerative disorders. Research indicates that enhancing antibody transport across the blood-brain barrier via TFR1, by forming specific bispecific antibodies with anti-β-amyloid antibodies, can improve therapeutic outcomes in Alzheimer's patients ^[4-5]. As research progresses, TFR1 is expected to become an effective clinical target for multiple diseases and a synergistic target for drug delivery across the blood-brain barrier (BBB). The hTFRC mouse model was generated by inserting the human TFRC gene sequence into the mouse Tfrc gene locus using gene-editing technology. To minimize interference from mouse gene sequences or proteins, part of the mouse Tfrc gene sequence was knocked out, resulting in a model expressing only the human TFR1 protein. This model is valuable for studying iron metabolism disorders, neurodegenerative diseases, and tumor development, supporting the development of TFR1-targeted therapeutics and preclinical pharmacological evaluations. Compared with the genome humanized huTFRC mice (Cat. No.: C001860), the CDS humanized hTFRC mice in this datasheet (Cat. No.: C001584) exhibited higher TFRC-mediated delivery efficiency in the central nervous system (CNS) and presented an anemic phenotype.

The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[1]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[2]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis ^[1]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients ^[3]. As a target for antibody-mediated cancer therapy, TFR1 can be leveraged through two approaches: one involves the use of antibodies conjugated to anti-cancer drugs, which are indirectly internalized via receptor-mediated endocytosis; the other employs antibodies that directly disrupt receptor function or induce Fc effector functions such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Various clinical drugs targeting TFR1 are currently under development, including antisense oligonucleotides (ASOs), antibody-drug conjugates (ADCs), and antibody-oligonucleotide conjugates, applicable to diseases such as cancer, anemia, and neurodegenerative disorders. Research indicates that enhancing antibody transport across the blood-brain barrier via TFR1, by forming specific bispecific antibodies with anti-β-amyloid antibodies, can improve therapeutic outcomes in Alzheimer's patients ^[4-5]. As research progresses, TFR1 is expected to become an effective clinical target for multiple diseases and a synergistic target for drug delivery across the blood-brain barrier (BBB). The huTFRC mouse model was generated by replacing the mouse Tfrc endogenous extracellular domain with the human TFRC extracellular domain. The murine cytoplasmic and helical will be kept. This model is valuable for studying iron metabolism disorders, neurodegenerative diseases, and tumor development, supporting the development of TFR1-targeted therapeutics and preclinical pharmacological evaluations. Compared with the CDS humanized hTFRC mice (Cat. No.: C001584), huTFRC mice (Cat. No.: C001860) exhibited normal serum iron levels, while the TFRC-mediated delivery efficiency in the central nervous system (CNS) was lower than that of hTFRC mice (Cat. No.: C001584).

Complement component C3 plays a central role in activating the complement system and is the most abundant complement protein in human plasma, primarily synthesized in the liver. As part of the innate immune system, the complement system is activated during tissue damage and pathogen invasion, playing a crucial role in the inflammatory response, host homeostasis, and pathogen defense. The complement cascade is activated through the classical pathway, alternative pathway, and lectin pathway, all of which generate C3 convertase, which cleaves C3 into C3a and C3b. C3a is a potent anaphylatoxin with pro-inflammatory activity, while C3b is a regulator that induces C5 cleavage, thereby participating in the dissolution and clearance of immune complexes. Mutations in this gene are associated with atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). Deficiencies in C3 and C3-derived peptides can lead to autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, and vasculitis) and make individuals susceptible to recurrent respiratory infections and infections caused by encapsulated organisms. Conversely, excessive activation of C3 and related complement components is associated with kidney diseases (immune complex glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, membranous nephropathy, and immune-mediated nephropathy) ^[1-2]. The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[3]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[4]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis ^[3]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients ^[5]. Various clinical drugs targeting TFR1 are currently under development, including antisense oligonucleotides (ASOs), antibody-drug conjugates (ADCs), and antibody-oligonucleotide conjugates, applicable to diseases such as cancer, anemia, and neurodegenerative disorders. Research indicates that enhancing antibody transport across the blood-brain barrier via TFR1, by forming specific bispecific antibodies with anti-β-amyloid antibodies, can improve therapeutic outcomes in Alzheimer's patients ^[6-7]. As research progresses, TFR1 is expected to become an effective clinical target for multiple diseases and a synergistic target for drug delivery across the blood-brain barrier (BBB). The hTFRC/huC3 mouse model is a humanized model obtained by breeding huC3 mice (Catalog No.: C001955) with hTFRC mice (Catalog No.: C001584). This model can be used for research on complement-mediated diseases, iron metabolism disorders, neurodegenerative diseases, and tumor development, aiding in studying C3/TFRC-targeted drugs.

The ALB gene encodes albumin, mainly produced in the liver, and is the most abundant protein in human plasma, accounting for 60% to 65% of total plasma protein. The proprotein encoded by ALB is processed to produce a functional protein, and the EPI-X4 peptide derived from this protein is an endogenous inhibitor of the CXCR4 chemokine receptor. Albumin plays a role in regulating plasma colloid osmotic pressure, helping to maintain blood circulation and isolating and transporting many metabolites within the body, especially insoluble hydrophobic metabolites ^[1]. Human Serum Albumin (HSA) is an important carrier protein involved in the transport of a variety of endogenous molecules, including hormones, fatty acids, and metabolic products, as well as exogenous drugs. As a natural carrier protein, HSA has multiple ligand binding sites and a plasma half-life of up to 19 days, making it a promising drug carrier. Several HSA-based drug delivery systems have been approved for clinical trials ^[2-3]. In addition, albumin is also the main transporter of zinc, calcium, and magnesium in plasma, binding approximately 80% of all plasma zinc and approximately 45% of circulating calcium and magnesium, with an affinity ranking of zinc > calcium > magnesium ^[4]. Diseases associated with the ALB gene include hyperthyroxinemia, familial serum albumin abnormality, and analbuminemia ^[5]. The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[6]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[7]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis ^[6]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients ^[8]. B6-hALB/hTFRC mice are a dual gene humanized model of Alb and Tfrc, obtained by crossing B6-hALB (HSA) mice (Catalog number: C001492) with B6-hTFRC (CDS) mice (Catalog number: C001584). This model can be used for the development of ALB/TFRC-targeted therapeutic drugs, as well as for the research on drug development using human serum albumin (HSA) as a carrier or drug delivery across the blood-brain barrier (BBB), and for in vivo pharmacodynamic and pharmacokinetic studies.

hTFRC/Ttn-KO mouse model is a model obtained by breeding Ttn-KO mice (Catalog No.: S-KO-05587) with hTFRC mice (Catalog No.: C001584). This model can be utilized in research for hereditary muscle diseases such as familial dilated cardiomyopathy (DCM), early-onset myopathy, and muscular dystrophy, supporting the development of TFRC-targeted gene supplementation therapies. Homozygous knockout of the Ttn gene is lethal, whereas heterozygous Ttn-KO mice are viable and fertile.

Interleukin-1β (IL-1β), encoded by the IL1B gene, is a cytokine with potent pro-inflammatory activity that plays a central role in inflammatory responses and innate immune regulation. It induces the release of various inflammatory mediators and activates immune cells, participating in the regulation of biological processes such as cell proliferation, differentiation, apoptosis, and febrile responses ^[1-2]. Studies have shown that abnormal expression or activity of IL-1β is closely associated with various pathological processes, including cryopyrin-associated periodic syndromes (CAPS), gout, rheumatoid arthritis (RA), recurrent pericarditis, type 2 diabetes mellitus (T2DM), and other inflammatory and autoimmune diseases, while also playing an important role in the pathogenesis of multiple malignancies and neurodegenerative diseases ^[3-4]. Transferrin receptor 1 (TFRC) is a transmembrane protein widely expressed across diverse cells and tissues, playing a critical role in iron transport and the maintenance of iron homeostasis. It is highly expressed on brain capillary endothelial cells, making it a vital target for drug delivery across the blood-brain barrier (BBB) ^[5-6]. In recent years, TFRC-mediated receptor-mediated transcytosis (RMT) has become a key strategy for improving the delivery efficiency of therapeutic antibodies and other macromolecular drugs across the BBB. In neuroinflammatory diseases such as multiple sclerosis (MS), IL-1β can promote microglial activation, induce pathogenic Th17 cell responses, increase BBB permeability, and facilitate the recruitment of inflammatory cells, thereby driving central nervous system inflammation and demyelinating injury ^[7-8]. The huIL1B/huTFRC mouse is a dual-gene humanized model obtained by crossing the huIL1B mouse (Catalog No.: C001791) with the huTFRC mouse (Catalog No.: C001860). This model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of IL1B/TFRC-targeted drugs. Meanwhile, it is suitable for evaluating the trans-BBB delivery capacity of therapeutic agents, providing an ideal preclinical research platform for the development of innovative therapies for neuroinflammatory diseases, such as multiple sclerosis (MS).

Myotonic dystrophy type 1 (DM1) is a rare, multisystemic disorder caused by mutations in the DMPK gene. Patients exhibit highly diverse clinical manifestations across multiple systems, primarily including peripheral skeletal muscle atrophy, cardiac conduction defects, insulin resistance, as well as central nervous system (CNS) complications (such as cognitive impairment and hypersomnia) ^[1]. Transferrin receptor 1 (TFRC) features a distinct expression and tissue distribution profile in vivo, serving as a critical receptor vehicle for the peripheral and central targeted delivery of current nucleic acid therapeutics. In the peripheral system, TFRC is highly expressed on the surface of skeletal muscle and myocardial cells, and has been successfully utilized to develop antibody-oligonucleotide conjugates (e.g., AOC 1001) designed for targeted DMPK silencing in muscles; in the central nervous system, TFRC is expressed on brain capillary endothelial cells, making it a core target for studying receptor-mediated transcytosis (RMT) across the blood-brain barrier (BBB). The huDMPK/huTFRC mouse is a dual-gene humanized model obtained by crossing the huDMPK mouse (Catalog No.: C001882) with the huTFRC mouse (Catalog No.: C001860). This model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of dual-target therapeutics against DMPK/TFRC, as well as comprehensive research on myotonic dystrophy type 1 (DM1) and its associated complications, including muscle atrophy, cardiac conduction abnormalities, insulin resistance, and central nervous system pathology.

The huGPR75/huTFRC mouse is a dual-gene humanized model obtained by mating the huGPR75(2) mouse (catalog No.: C001614) with the huTFRC mouse (catalog No.: C001860). This model can be used for the research on the pathological mechanisms and treatment methods of obesity, metabolic diseases, and cardiovascular diseases, as well as the development of GPR75/TFRC-targeted drugs.