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.

Frontotemporal Dementia (FTD) is the second most prevalent form of early-onset dementia, following Alzheimer’s disease (AD). This condition is distinguished by the selective degeneration of the frontal and temporal lobes, resulting in personality and behavioral changes, language impairments, and executive dysfunction. Approximately 40%-50% of FTD cases have a familial component, with known causative genes including MAPT, FUS, and TARDBP. Of these, MAPT is the earliest discovered and most frequently implicated in FTD. Mutations in the MAPT gene are detectable in roughly 30% of familial FTD cases ^[1]. 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 ^[2]. 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 ^[3-4]. Therapies targeting the MAPT gene primarily consist of small-molecule drugs and monoclonal antibodies, with indications including AD and FTD. Transgenic mice are frequently used in the drug development process, and the utilization of humanized animal models can facilitate the translation of promising treatments into clinical trials ^[5-9]. This strain is a humanized mouse model in which the endogenous mouse Mapt gene has been replaced with its human counterpart, including the 3’UTR region. This model can be utilized to study various neurodegenerative diseases, such as FTD and AD. This model is commonly named htau. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.

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]. 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). Parkinson's disease (PD) is a neurodegenerative disease with a high prevalence mainly in the middle-aged and elderly population. It is the second most common neurodegenerative disease after Alzheimer's disease (AD). The main clinical symptoms include resting tremors, limb stiffness, bradykinesia, loss of voluntary movement, etc. The typical pathological process of PD is the formation of Lewy bodies (LB) in the central nervous system (CNS), which results in the gradual death and loss of dopaminergic neurons, leading to the disease ^[6-7]. The main components of Lewy bodies are insoluble aggregates of abnormal α-synuclein (α-syn), and the SNCA gene, which encodes α-synuclein, is one of the key causative genes in Parkinson's disease. Mutations in this gene cause overexpression of α-syn, leading to the formation of Lewy bodies, ultimately leading to PD ^[8]. In addition, SNCA mutations are also associated with diseases such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). B6-huTFRC/huSNCA(3'UTR) mice are a dual-gene humanized model generated by crossing B6-huTFRC mice (Catalog No.: C001860) with B6-hSNCA (3'UTR) mice (Catalog No.: C001698). This model can be used for research on neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), as well as iron metabolism disorders and tumorigenesis and development. It is also applicable for the development of TFRC/SNCA-targeted drugs.

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)*Del E50 mouse is a humanized model of the Dmd gene, in which the genomic sequences corresponding to exons 49–53 and their flanking regions in the mouse Dmd gene have been replaced with the corresponding human DMD gene sequences, followed by knock-out of exon 50 in the human DMD gene within the mouse genome. This model is suitable for research on Duchenne muscular dystrophy. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen provides other humanized models such as [hE49-53], [hE44-45, c.6438+2 T to A], [hE8-30], covering most popular research areas and offering customized services based on different mutation needs.

The MSH3 gene is a critical component of the post-replicative DNA mismatch repair (MMR) system that maintains genomic stability. It encodes the MSH3 protein, which serves as a housekeeping protein and is ubiquitously expressed at low levels across a wide range of human tissues, including the colon, rectum, small intestine, brain, and reproductive organs ^[1]. The protein primarily functions by forming a heterodimer with MSH2 to create the MutSβ complex, which is specialized in recognizing and initiating the repair of large insertion-deletion loops (IDLs) and dinucleotide or longer microsatellite repeats. Beyond its canonical MMR role, MSH3 is involved in homologous recombination and the repair of DNA double-strand breaks, contributing to cellular resistance against platinum-based chemotherapeutics ^[2]. Furthermore, MSH3 has been identified as a key genetic modifier of repeat expansion diseases, such as Huntington’s disease and myotonic dystrophy type 1, where its activity paradoxically promotes the somatic expansion of toxic CAG/CTG repeats, thereby influencing disease onset and progression ^[3]. The B6-huMSH3 mouse is a humanized model constructed through gene-editing technology, in which the exon 7 to downstream of exon 24 of mouse Msh3 is replaced with the entire human MSH3 gene plus human MSH3 promoter and downstream region, and the human sequence is inserted in reverse to prevent disruption of the Dhfr gene function. This model can be used for research on Huntington’s disease (HD) and myotonic dystrophy type 1 (DM1), as well as for screening, development, and preclinical evaluation of MSH3-targeted therapeutics.

The Sez6 gene primarily encodes a Seizure-related homolog protein 6 (SEZ6), a cell-surface type I transmembrane glycoprotein that is an N-glycosylated protein containing five short consensus repeat (SCR)/sushi domains and two or three CUB domains in its extracellular domain ^[1]. Gene expression is highly restricted in normal adult tissues, found almost exclusively in the central nervous system (CNS), particularly in neurons (e.g., in the cerebral cortex, hippocampus), with low expression in the testis and some gastrointestinal tissues. SEZ6 is involved in neuronal development and function, notably in regulating dendrite elongation and branching, synaptic plasticity, and may also function as a complement regulator by inhibiting C3 convertases, in addition to being a novel trafficking protein of the kainate receptor (KAR) ^[2]. Associated diseases include neurodevelopmental and psychiatric disorders such as epilepsy (especially febrile seizures), schizophrenia, and Alzheimer's disease. Furthermore, SEZ6 overexpression has been detected in various high-grade neuroendocrine malignancies (e.g., small cell lung cancer (SCLC), medullary thyroid carcinomas), making it a novel therapeutic target in cancer ^[1]. The B6-hSEZ6 mouse is a humanized model constructed by gene-editing technology, in which the p.20 to partial intron 3 of mouse Sez6 is replaced with Human-Mouse chimeric CDS (Human SEZ6 Extracellular + Mouse Sez6 Intracellular)-3'UTR of Mouse Sez6-WPRE-BGH pA cassette. The murine signal peptide is remained. This model can be used for the research of the pathological mechanisms of neurodevelopmental and psychiatric disorders such as epilepsy (especially febrile seizures), schizophrenia, and Alzheimer's disease, and some cancers, as well as the development of relevant treatment methods, and the screening, development, and pre-clinical evaluation of SEZ6-targeted drugs.

The B6-huTFRC/huACVR2B mouse is a dual-gene humanized model obtained by mating B6-huTFRC mice (catalog No.: C001860) with B6-huACVR2B mice (catalog No.: C001904). This model can be used in the research of muscle atrophy and growth regulation, tumorigenesis and development, reproduction and gonadal function, iron metabolism diseases, and neurodegenerative diseases, and it helps with the development of TFRC/ACVR2B-targeted drugs and preclinical pharmacological and efficacy evaluations.

The B6-huGDF8/huTFRC mouse is a dual-gene humanized model obtained by mating B6-huMSTN (huGDF8) mice (catalog No.: C001636) with B6-huTFRC mice (catalog No.: C001860). Transferrin receptor 1 (TFR1 or TFRC) is highly expressed in brain endothelial cells and muscle cells. It can be used as a target for receptor-mediated transcytosis (RMT) to achieve efficient transport of macromolecular drugs across the blood-brain barrier (BBB) and into muscle tissues. This model can be used for research on the pathological mechanisms and treatment methods of muscular atrophy, sarcopenia, metabolic syndrome, and iron metabolism diseases, as well as for the development of MSTN/TFRC targeted drugs.

The B6-huTFRC/huACVR2A mouse is a dual-gene humanized model obtained by mating B6-huTFRC mice (catalog No.: C001860) with B6-huACVR2A mice (catalog No.: C001903). This model can be used in relevant research on malignant tumors such as colorectal cancer and gastric cancer, iron metabolism diseases, neurodegenerative diseases, reproductive system and gonadal development, etc., and it helps with the development of TFRC/ACVR2A-targeted drugs and preclinical pharmacological and efficacy evaluations.

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.