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)*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 DMPK gene provides instructions for producing dystrophia myotonica protein kinase, a serine/threonine kinase that is primarily expressed in skeletal muscle, cardiac muscle, and the central nervous system, with lower levels found in smooth muscle and other tissues. This protein serves as a critical regulator of cellular processes, including the maintenance of muscle structure, ion channel gating (specifically sodium and calcium channels), and intracellular signaling pathways related to cytoskeletal dynamics and mitochondrial health. The gene is famously associated with Myotonic Dystrophy Type 1 (DM1), a multisystemic disorder caused by an unstable CTG trinucleotide repeat expansion in the 3' untranslated region (3'UTR) ^[1]. In healthy individuals, this sequence repeats between 5 and 37 times, but pathogenic expansions exceeding 50 repeats—sometimes reaching thousands—lead to the production of toxic "gain-of-function" RNA ^[2]. This mutant RNA accumulates in nuclear foci, sequestering critical splicing proteins (like MBNL1) and resulting in a wide array of clinical features, including progressive muscle wasting, myotonia (the inability to relax muscles), cardiac conduction defects, cataracts, and endocrine dysfunctions such as insulin resistance ^[3]. The B6-huDMPK mouse is a humanized model constructed through gene-editing technology, in which the sequences upstream of exon 1 to intron 10 of the mouse Dmpk gene are replaced with the sequences from upstream of exon 1 to downstream of the human DMPK gene. This model can be used for research on Myotonic Dystrophy Type 1 (DM1), cardiac conduction defects, cataracts, and endocrine dysfunctions such as insulin resistance, as well as for screening, development, and preclinical evaluation of DMPK-targeted therapeutics.

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.

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.