Angiopoietin-like protein 4 (ANGPTL4) is a member of the angiopoietin-like protein family and is highly expressed in metabolically active organs and tissues, such as the liver, adipose tissue, and small intestine ^[1]. As a physiological inhibitor of lipoprotein lipase (LPL), ANGPTL4 non-covalently binds to and inhibits LPL activity primarily through its N-terminal domain, thereby blocking the peripheral hydrolysis and clearance of triglyceride-rich lipoproteins (e.g., chylomicrons and very-low-density lipoprotein remnants) and participating in the regulation of systemic lipid metabolism and triglyceride homeostasis ^[2]. Studies have demonstrated that the dysfunction of ANGPTL4 is closely associated with obesity, type 2 diabetes (T2D), hypertriglyceridemia, atherosclerotic cardiovascular disease (ASCVD), metabolic dysfunction-associated steatotic liver disease (MASLD), and microenvironmental remodeling in malignancies such as triple-negative breast cancer, making it an important drug discovery target in metabolic disorders, cardiovascular diseases, and oncology translational medicine ^[2-5]. The huANGPTL4 mouse is a humanized model developed via gene editing technology, in which the sequence of the endogenous mouse Angptl4 gene from the start codon to the stop codon is replaced with the corresponding sequence of the human ANGPTL4 gene. This model is applicable for pathological mechanism studies of lipid metabolism disorders, organ fibrosis, and related malignancies, as well as for the screening, development, and preclinical in vivo evaluation of neutralizing antibodies, small molecule inhibitors, and nucleic acid drugs targeting human ANGPTL4.

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 huDMD(E44-45, dp140del)-DelE44 mouse is a humanized model of the Dmd gene, where exons 44-45 and the flanking regions of the mouse Dmd gene are replaced with the corresponding sequences of exon 45 and its flanking regions from the human DMD gene (i.e., exon 44 of the human DMD gene is deleted). This model is suitable for researching Duchenne Muscular Dystrophy. Internal testing revealed that the deletion of intron 44 leads to the absence of the brain-specific DMD isoform dp140, which may potentially confound behavioral data. Therefore, we do not recommend using this strain for behavioral studies. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen provides other humanized models such as [hE49-53, del E50], [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.

C-C motif chemokine ligand 1 (CCL1), also known as I-309, is a small chemokine mainly secreted by activated T cells, monocytes, and endothelial cells. It belongs to the CC chemokine family and plays a key regulatory role in Th2-type immune responses and the recruitment of regulatory T cells (Tregs) ^[1]. CCL1 binds to its specific receptor CCR8 (C-C chemokine receptor type 8) to mediate the directed migration of Th2 cells and Tregs to inflammatory sites and the tumor microenvironment, promoting the formation of an immunosuppressive tumor microenvironment (TME). It is also involved in the immune regulation of allergic inflammatory responses, autoimmune diseases, and graft-versus-host disease (GvHD) ^[2-3]. The CCL1 gene is located on human chromosome 17 (17q12) and is closely associated with immune evasion in various solid tumors, Th2-type allergic diseases, and the development of inflammatory bowel disease (IBD). Targeting the CCL1-CCR8 signaling axis has become an important strategy for drug development in tumor immunotherapy, allergic diseases, and autoimmune disorders ^[4-5]. The huCCL1(BALB/c) mouse is a humanized model constructed through gene editing technology. The sequences from the start codon to the stop codon of the endogenous mouse Ccl1 gene were replaced with the sequences from the start codon to the stop codon of the human CCL1 gene. This model is suitable for evaluating the efficacy and safety of CCL1-targeted antibodies and CAR-T/CAR-NK cell therapies, as well as for preclinical research in tumor immunity, Th2/Treg immune regulation, allergic disorders, and autoimmune diseases.

Interleukin-18 (IL18) is a pro-inflammatory cytokine primarily secreted by macrophages, dendritic cells, and keratinocytes. It is a member of the IL-1 superfamily and plays an important regulatory role in both innate and adaptive immune responses ^[1]. IL18 binds to the IL18 receptor (IL18R) and, in synergy with IL12, induces Th1 cells to produce interferon-γ (IFN-γ), promoting the activation and proliferation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, while also participating in the regulation of inflammasome-mediated inflammatory responses ^[2-3]. The IL18 gene is located on human chromosome 11 and is closely associated with the development of various autoimmune diseases, infectious diseases, and cancers. It has emerged as an important target for tumor immunotherapy, infectious vaccine development, and drug research for autoimmune diseases ^[4-5]. The huIL18 mouse is a humanized model constructed by gene-editing technology, in which the sequence from the start codon to the stop codon of the mouse endogenous Il18 gene is replaced with the corresponding sequence of the human IL18 gene. This model is suitable for evaluating the efficacy and safety of IL18-targeted antibodies and CAR-cell therapies, as well as for preclinical studies in tumor immunity, infectious disease vaccines, autoimmune disorders, and metabolic and cardiovascular diseases.

The TNFRSF13B gene encodes the transmembrane activator and CAML interactor (TACI), a receptor belonging to the tumor necrosis factor receptor superfamily, predominantly expressed on B lymphocytes. TACI plays a critical role in humoral immunity by recognizing the TNF ligands B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) ^[1]. Upon ligand binding, TACI modulates intracellular signaling pathways, including NFAT, AP1, and NF-κB, which are essential for B cell survival, maturation into plasma cells, and the production of immunoglobulins ^[2]. Notably, TNFRSF13B is highly polymorphic, and specific genetic variants are strongly associated with the pathogenesis of common variable immunodeficiency (CVID), a primary immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection ^[3]. While the precise mechanisms by which these variants contribute to disease are still under investigation, they often result in impaired TACI function, disrupting normal B cell development and antibody responses ^[4]. Further research into the regulation and function of TACI is crucial for understanding the complex etiology of CVID and for developing targeted therapeutic strategies for this and potentially other immune-related disorders. The hTACI(TNFRSF13B) mouse is a humanized model constructed by replacing the exon 2 plus partial intron 2 of the mouse Tnfrsf13b gene in situ with the Kozak-TNFRSF13B chimeric CDS-3'UTR of mouse Tnfrsf13b-WPRE-BGH pA cassette. The hTACI(TNFRSF13B) mice can be used for studies on common variable immunodeficiency (CVID), and pathogenesis of immune-related diseases, as well as for TNFRSF13B-targeted drug development.

STEAP1 (Six transmembrane epithelial antigen of the prostate 1) is a member of the six-transmembrane epithelial antigen family encoded by the STEAP1 gene and is primarily localized on the cell membrane surface. STEAP1 is highly expressed in multiple solid tumors, including prostate cancer, Ewing sarcoma, bladder cancer, and lung cancer, while its expression in normal tissues is relatively restricted ^[1-3]. STEAP1 is involved in biological processes including cell proliferation, redox homeostasis, and regulation of the tumor microenvironment, and has been associated with tumor invasion, metastasis, and poor prognosis in multiple malignancies ^[2-4]. Due to its tumor-associated high expression pattern and membrane localization, STEAP1 is considered an important target for cancer immunotherapy. Studies involving STEAP1-targeted monoclonal antibodies, antibody-drug conjugates (ADCs), T-cell engagers (TCEs), and CAR-T/CAR-NK cell therapies have been reported ^[3-5]. The huSTEAP1 mouse is a humanized model generated by replacing the sequence of exons 2 to 5 in the murine Steap1 gene with the corresponding sequence of human STEAP1 exons 2 to 5. This model is suitable for evaluating the in vivo efficacy and safety of STEAP1-targeted therapeutics, including monoclonal antibodies, ADCs, TCEs, and CAR-T/CAR-NK cells. Furthermore, it is applicable to research on the pathogenesis of prostate cancer and other STEAP1-overexpressing tumors, as well as studies on the tumor immune microenvironment and combination therapy strategies.

Glypican-3 (GPC3) is a heparan sulfate proteoglycan encoded by the GPC3 gene, anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) moiety. It is widely expressed during embryonic development but is expressed at very low or nearly undetectable levels in normal adult liver tissues ^[1-2]. GPC3 is predominantly overexpressed in hepatocellular carcinoma (HCC) and hepatoblastoma, making it an important tumor-associated antigen ^[2-4]. The GPC3-encoded protein participates in the regulation of signaling pathways such as Wnt/β‑catenin, Hedgehog, and YAP, and plays critical roles in tumor cell proliferation, migration, invasion, and modulation of the tumor microenvironment ^[1,3]. Studies have shown that aberrant GPC3 expression is closely associated with poor prognosis, tumor metastasis, and recurrence in HCC ^[4]. Moreover, Gpc3 gene deletion or mutation can lead to neonatal lethality, embryonic overgrowth, and renal cysts ^[5]. Due to its low expression in normal adult tissues and high specificity in HCC, GPC3 has emerged as a key target for targeted therapy and cancer immunotherapy. To date, various GPC3‑directed therapeutic modalities, including CAR‑T cells, CAR‑NK cells, monoclonal antibodies, bispecific antibodies, and antibody‑drug conjugates (ADCs), have been developed for tumor immunotherapy ^[1,3-4,6]. The hGPC3 mouse is a humanized model generated by replacing a partial sequence of exon 1 in the murine Gpc3 gene with the Kozak-Human GPC3 CDS-3'UTR of Mouse Gpc3-WPRE-BGH pA cassette. This model is suitable for evaluating the in vivo efficacy and safety of GPC3-targeted therapeutics, including CAR-T/CAR-NK cells, monoclonal antibodies, bispecific antibodies, and ADCs. Furthermore, it is applicable to research on hepatocellular carcinoma (HCC) pathogenesis, the tumor immune microenvironment, and combination therapy strategies.