The ABCD1 (ATP-binding cassette subfamily D member 1) gene, located on the X chromosome (Xq28), encodes a peroxisomal transmembrane protein responsible for transporting very long-chain fatty acids (VLCFAs) into peroxisomes for β-oxidation. Widely expressed but particularly prominent in the brain, adrenal glands, and liver, ABCD1 is critical for maintaining lipid homeostasis. Mutations in ABCD1 cause X-linked adrenoleukodystrophy (X-ALD), a neurodegenerative disorder characterized by VLCFA accumulation, demyelination, adrenal insufficiency, and progressive neurological decline. Clinical manifestations vary widely, ranging from asymptomatic carriers to a severe, fatal childhood form. Primarily affecting males (with an estimated incidence of ~1 in 17,000 newborns), X-ALD has been included in newborn screening programs in many U.S. states ^[1-2]. The correlation between specific mutations and symptoms remains unclear, and VLCFA measurement cannot reliably predict disease-specific outcomes such as adrenal insufficiency or neurological decline. Current therapeutic approaches focus on gene repair or mitigating secondary effects like oxidative stress ^[3]. The Abcd1 KO mouse, a gene knockout model generated by deleting exon 2 of the mouse Abcd1 gene (homologous to human ABCD1), serves as a valuable tool for studying the pathogenesis of X-ALD and developing therapeutic interventions.

Duchenne Muscular Dystrophy (DMD) is a severe, progressive, and disabling X-linked recessive genetic disorder characterized primarily by muscle atrophy. This disease leads to motor impairments, eventually requiring assisted ventilation, and often results in premature death. The primary cause of DMD is mutations in the DMD gene, which encodes the dystrophin protein. These mutations lead to a reduction or absence of dystrophin in muscle tissue, resulting in muscle atrophy and related complications ^[1]. The lack of dystrophin leads to the breakdown of the dystrophin-associated protein complex (DAPC) within the muscle membrane, disrupting the interaction between actin and the extracellular matrix, making the muscles more susceptible to damage. This susceptibility results in the gradual loss of muscle tissue and function, potentially leading to cardiomyopathy ^[2]. Researchers have identified thousands of different DMD gene mutations in patients with DMD. Deletion mutations account for approximately 60%–70%, while duplication mutations account for 5%–15%. These mutations are primarily concentrated in hotspot regions of the DMD gene, specifically between exons 45-55 (47%) and exons 3-9 (7%) ^[1]. Currently, gene therapy approaches for Duchenne Muscular Dystrophy (DMD) primarily include exon skipping and AAV supplementation, as well as emerging gene editing techniques like CRISPR. The exon skipping strategy involves using antisense oligonucleotide (ASO) drugs to bind to specific sequences of pre-mRNA, skipping the mutated exon and restoring the open reading frame (ORF) integrity, thus producing a truncated but partially functional dystrophin protein. Several ASO drugs targeting the DMD gene have been approved, such as Eteplirsen (targeting exon 51), Golodirsen (targeting exon 53), and Casimersen (targeting exon 45) developed by Sarepta, and Viltolarsen (targeting exon 53) developed by Nippon Shinyaku. Since most ASO and CRISPR-based gene editing therapies target the human DMD gene, humanizing mouse genes helps accelerate clinical applications for DMD therapies, considering the genetic differences between animals and humans. The B6-hDMD (E49-53) mouse is a humanized model of exons 49-53 of the Dmd gene, used for researching Duchenne Muscular Dystrophy. Homozygotes are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen provides other humanized models such as [hE49-53, del E50], [hE44-45], [hE44-45, del E44], [hE44-45, c.6438+2 T to A], and [hE8-30], covering most popular research areas and offering customized services based on different mutation needs.

The protein encoded by the triggering receptor expressed on myeloid cells 2 (TREM2) gene can form a receptor signaling complex with TYRO protein tyrosine kinase-binding protein. This protein is mainly expressed in macrophages and dendritic cells, among which microglia in the central nervous system are the core cell types for its expression. The TREM2 protein binds to the adapter protein Dap-12, recruits various signaling molecules such as kinases and phospholipase C-γ, and assembles to form a receptor signaling complex, thereby activating myeloid cells such as microglia and dendritic cells. Functionally, TREM2 participates in innate and adaptive immune responses, regulates the chronic inflammatory process by inducing the production of inflammatory cytokines, and it has been confirmed to be associated with colonic wound healing ^[1]. Genetic studies have shown that mutations in the TREM2 gene are one of the pathogenic factors for polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), and variations in this gene are closely related to an increased risk of neurodegenerative diseases such as Alzheimer's disease (AD) ^[2]. Tumor-associated macrophages (TAMs) are involved in the tumor's resistance to the immune system, and TREM2 plays a role in TAMs and myeloid-derived suppressor cells (MDSCs), with its expression level being positively correlated with tumor progression ^[3]. The B6-huTREM2 mouse is a humanized model constructed by gene-editing technology, in which the sequence from the upstream of exon 1 to the downstream of exon 5 of the mouse Trem2 gene is replaced with the corresponding sequence of the human TREM2 gene. This model can be used for the research of the pathological mechanisms of Alzheimer's disease (AD), polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), and some cancers, as well as the development of relevant treatment methods, and the screening, development, and pre-clinical evaluation of TREM2-targeted drugs.

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 tau protein, a microtubule-associated protein encoded by MAPT, is primarily localized to neuronal axons and plays a critical role in microtubule stability and assembly. By binding to microtubules, the tau protein helps to maintain neuronal cell shape. Mutations in MAPT can promote tau aggregation, leading to pathological tau protein accumulation and death of glutamatergic cortical neurons ^[6]. Additionally, certain MAPT mutations can affect pre-mRNA exon splicing, altering the ratio of 3R to 4R tau protein isoforms and increasing the relative production of 4R-tau protein, which is more prone to fibril formation ^[7-8]. The B6-huTFRC/htau mouse is a dual-gene humanized model obtained by mating B6-huTFRC mice (catalog number: C001860) with B6-htau mice (catalog number: C001410). This model can be used for research on neurodegenerative diseases and iron metabolism diseases, as well as pre-clinical studies of TFRC/MAPT-targeted therapeutic drugs.

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 tau protein, a microtubule-associated protein encoded by MAPT, is primarily localized to neuronal axons and plays a critical role in microtubule stability and assembly. By binding to microtubules, the tau protein helps to maintain neuronal cell shape. Mutations in MAPT can promote tau aggregation, leading to pathological tau protein accumulation and death of glutamatergic cortical neurons ^[6]. Additionally, certain MAPT mutations can affect pre-mRNA exon splicing, altering the ratio of 3R to 4R tau protein isoforms and increasing the relative production of 4R-tau protein, which is more prone to fibril formation ^[7]. Common mutations include P301L, P301S, and Intron10+3 G>A ^[8]. The B6-huTFRC/htau*P301L mouse is a humanized disease model obtained by mating B6-huTFRC mice (catalog number: C001860) with B6-htau*P301L mice (catalog number: C001835). This model can be used for the research of Alzheimer's disease (AD), frontotemporal dementia (FTD), neurodegenerative diseases, and tumorigenesis and development, as well as the development of TFRC/MAPT-targeted drugs.

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 tau protein, a microtubule-associated protein encoded by MAPT, is primarily localized to neuronal axons and plays a critical role in microtubule stability and assembly. By binding to microtubules, the tau protein helps to maintain neuronal cell shape. Mutations in MAPT can promote tau aggregation, leading to pathological tau protein accumulation and death of glutamatergic cortical neurons ^[6]. Additionally, certain MAPT mutations can affect pre-mRNA exon splicing, altering the ratio of 3R to 4R tau protein isoforms and increasing the relative production of 4R-tau protein, which is more prone to fibril formation ^[7]. Common mutations include P301L, P301S, and Intron10+3 G>A ^[8]. The B6-huTFRC/htau*P301S mouse is a humanized disease model obtained by mating B6-huTFRC mice (catalog number: C001860) with B6-htau*P301S mice (catalog number: C001836). This model can be used for the research of Alzheimer's disease (AD), frontotemporal dementia (FTD), neurodegenerative diseases, and tumorigenesis and development, as well as the development of TFRC/MAPT-targeted drugs.

The amyloid beta precursor protein (APP) gene encodes a transmembrane precursor protein that acts as a cell surface receptor. This protein is cleaved by secretase to form a polypeptide, part of which forms the protein basis for beta-amyloid plaques (Aβ) found in the brains of Alzheimer’s disease (AD) patients. Mutations in the APP gene are associated with autosomal dominant Alzheimer’s disease and cerebral amyloid angiopathy (CAA) ^[1]. The presenilin 1 (PS1) gene encodes presenilin, which regulates the processing of APP through its action on γ-secretase, a protease responsible for cleaving the APP precursor. Presenilin is also involved in the cleavage of Notch receptors. Mutations in the PS1 or APP genes are found in patients with hereditary Alzheimer’s disease (AD). These disease-associated mutations typically result in an increase in the longer form of β-amyloid protein, the main component of amyloid deposits found in the brains of AD patients ^[2]. 5xFAD mouse rapidly reproduces the main features of AD amyloid pathology and exhibits behavioral defects at different stages, presenting AD-like and progressive cerebral amyloid angiopathy (CAA)-like phenotypes. It is a useful model for studying Aβ42-induced neurodegeneration and amyloid plaque formation within neurons ^[3-4]. 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 ^[5]. 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 ^[6]. 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 ^[5]. 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 ^[7]. 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 ^[8-9]. 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 B6-huTFRC/5xFAD mice are an Alzheimer's disease research model obtained by mating B6-huTFRC mice (catalog number: C001860) with 5xFAD mice (catalog number: C001541). This model can be used for the research of neurodegenerative diseases such as Alzheimer's disease (AD) and the development and efficacy evaluation of AD treatment strategies targeting TFRC.

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal progressive neurodegenerative disease. The disease is caused by the degeneration and death of motor neurons that control skeletal muscles in the central nervous system, leading to gradual muscle weakness and atrophy, and ultimately complete loss of voluntary movement control by the brain ^[1]. Unlike Alzheimer’s disease, ALS does not necessarily affect higher brain functions. On the contrary, late-stage patients can maintain clear thinking and retain memories, personality, and intelligence before the onset of the disease. The known ALS-causing genes include SOD1, ALS2, TARDBP, and FUS, among others. FUS is a multifunctional DNA/RNA-binding protein that is usually localized within the nucleus but can also shuttle between the nucleus and the cytoplasm. The FUS protein plays an important role in processes such as RNA transcription, splicing, and microRNA processing. Mutations in the FUS gene are closely associated with frontotemporal lobar degeneration/dementia (FTLD-FUS) and amyotrophic lateral sclerosis (ALS-FUS). Typically, the histopathological feature of ALS-FUS patients is the mislocalization of the FUS protein to the cytoplasm in spinal cord neurons and glial cells, and the formation of FUS-positive inclusions. However, based on current cases, only a portion of patients exhibit FUS mislocalization, and changes in the nuclear function of FUS mutants can also trigger ALS. Pathological FUS mice can induce neurodegeneration in the absence of cytoplasmic pathological changes or even significant mislocalization, which strongly indicates that the toxic nuclear function of FUS mutants may be a potential pathogenic mechanism. More than 50 FUS gene mutations have been found in patients with familial ALS and sporadic ALS, and the vast majority of them are inherited in an autosomal dominant pattern ^[2]. The mutant FUS protein generated by the R521C mutation in the FUS gene can form a stable complex with the wild-type (WT) FUS protein, interfere with normal protein interactions, cause DNA damage, and exhibit abnormal dendritic and synaptic phenotypes in the mouse brain and spinal cord. There is evidence that FUS-R521C mice have defects in transcription and splicing of genes responsible for regulating dendritic growth and synaptic function ^[3]. The FUS-targeted drugs under research are mainly gene therapy drugs, such as antisense oligonucleotides (ASOs). The ASO drug (ION363) developed by Ionis has entered phase 3 clinical trials. This drug can effectively reduce the abnormal expression of FUS in diseased mice ^[4]. Most gene therapy methods act on human genes. Considering the genetic differences between animals and humans, humanizing the mouse genes will help accelerate the advancement of FUS-targeted gene therapies into the clinical stage. This model is a humanized model. Gene editing technology is used to replace the endogenous mouse Fus gene with a human FUS gene fragment carrying the R521C mutation. B6-hFUS*R521C mice can be used for the research of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration/dementia (FTLD). In addition, based on the technological innovation of TurboKnockout fusion BAC recombination independently developed by Cyagen, customized services can be provided for different point mutations to meet the experimental needs of researchers.

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal progressive neurodegenerative disease. The disease is caused by the degeneration and death of motor neurons that control skeletal muscles in the central nervous system, leading to gradual muscle weakness and atrophy, and ultimately complete loss of voluntary movement control by the brain ^[1]. Unlike Alzheimer’s disease, ALS does not necessarily affect higher brain functions. On the contrary, late-stage patients can maintain clear thinking and retain memories, personality, and intelligence before the onset of the disease. The known ALS-causing genes include SOD1, ALS2, TARDBP, and FUS, among others. FUS is a multifunctional DNA/RNA binding protein typically located in the cell nucleus and can shuttle between the nucleus and cytoplasm. FUS protein plays an important role in RNA transcription, splicing, and microRNA processing. Mutations in the FUS gene are closely related to frontotemporal lobar degeneration/dementia (FTLD-FUS) and amyotrophic lateral sclerosis (ALS-FUS). More than 50 FUS gene mutations have been identified in familial and sporadic ALS patients, most of which are autosomal dominant and most of which affect the nuclear localization signal (NLS) of FUS protein ^[2]. ALS-FUS patients have a histopathological feature of FUS protein mislocalization to the cytoplasm and formation of FUS-positive inclusions in spinal motor neurons and glial cells. However, in current cases, only some patients exhibit FUS mislocalization, and changes in the nuclear function of FUS mutants can also cause ALS. Studies have found that FUS pathological mice can induce neurodegeneration without cytoplasmic pathology or obvious mislocalization, which strongly suggests that the nuclear toxic function of FUS mutants may be a potential pathogenic mechanism ^[2]. Most FUS-targeting drugs in development are gene therapies, including antisense oligonucleotides (ASOs). The ASO drug ION363 developed by Ionis Pharmaceuticals can effectively reduce abnormal expression of FUS in diseased mice ^[3]. Humanizing mouse genes, given the genetic differences between animals and humans, can accelerate the development of FUS-targeted gene therapy for clinical use. This strain is a mouse Fus gene humanized model and can be used for research on ALS. The homozygous B6-hFUS mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain (e.g. FUS (p.R521C)) and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields related to ALS.

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]. The tau protein, a microtubule-associated protein encoded by MAPT, is primarily localized to neuronal axons and plays a critical role in microtubule stability and assembly. By binding to microtubules, the tau protein helps to maintain neuronal cell shape. Mutations in MAPT can promote tau aggregation, leading to pathological tau protein accumulation and death of glutamatergic cortical neurons ^[4]. Additionally, certain MAPT mutations can affect pre-mRNA exon splicing, altering the ratio of 3R to 4R tau protein isoforms and increasing the relative production of 4R-tau protein, which is more prone to fibril formation ^[5]. The B6-hTFRC/htau mice are a model expressing human TFRC protein and tau protein, generated by crossing B6-hTFRC(CDS) mice (Catalog No.: C001584) with B6-htau mice (Catalog No.: C001410). These mice can be used for research on neurodegenerative diseases and iron metabolism disorders, as well as for the development and preclinical evaluation of TFRC/MAPT-targeted therapeutic agents.