The CD19 gene encodes a member of the immunoglobulin gene superfamily. As a key co-receptor in the B cell receptor (BCR) signaling pathway, it is crucial for B cell development, activation, and differentiation. CD19, a pan-B-cell marker exclusively expressed in the B cell lineage, remains stable throughout B cell development, from pro-B cells to mature and memory B cells. It acts as a positive regulator of BCR signal transduction by forming a B cell-specific signaling complex with CD21 (complement receptor 2), CD81 (tetraspanin), and CD225 (Leu13), which lowers the threshold for antigen-induced B cell activation ^[1]. Dysregulation of CD19 is strongly linked to autoimmune diseases such as systemic lupus erythematosus (SLE) and B cell malignancies like acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma. Mutations in this gene are associated with common variable immunodeficiency 3 (CVID3), characterized by impaired B cell differentiation and hypogammaglobulinemia. Owing to its B cell-specific expression, CD19 has become a pivotal target for immunotherapy. For example, anti-CD19 CAR-T cell therapy (e.g., Tisagenlecleucel) has shown remarkable efficacy in refractory or relapsed ALL ^[2]. Recent studies have also explored CD19-targeted bispecific antibodies (e.g., blinatumomab) to enhance tumor cell clearance ^[3]. huCD19 mice are a humanized model generated by replacing the mouse endogenous Cd19 gene sequence from the ATG start codon to part of intron 4 with the corresponding human CD19 gene sequence using gene editing technology. This model is applicable for studying B cell development and function, as well as therapeutic research on autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and B cell malignancies. It is an ideal research platform for preclinical efficacy evaluation of anti-human CD19 CAR-T cell therapy, and the development of bispecific antibodies and combination therapies.

Epilepsy, a chronic neurological disorder, is diagnosed in an estimated 5 million individuals globally each year. An epileptic seizure may result in brief involuntary convulsions, occasionally accompanied by loss of consciousness and urinary incontinence. Patients with epilepsy often face additional physical complications and psychological disorders. The risk of premature death for patients with epilepsy can be tripled, with the highest rates observed in low- and middle-income countries and rural areas ^[1]. The etiology of epilepsy is multifactorial, encompassing structural, genetic, infectious, metabolic, and immune factors. With the advent of genetic testing in pediatric neurology, a genetic cause is believed to underlie more than half of pediatric epilepsy cases. Voltage-gated sodium ion channel genes, including SCN1A, SCN2A, SCN3A, and SCN8A, are implicated in epilepsy. Single nucleotide variations (SNVs) can result in either loss or gain of function of the affected ion channels, such as in the case of epileptic encephalopathies (DEEs) associated with SCN2A ^[2-4]。 The SCN2A gene, encoding the α2 subunit of the voltage-gated sodium channel (Nav1.2), is a significant contributor to epilepsy. Mutations in SCN2A are associated with various neurological disorders and are inherited in an autosomal dominant manner. Current epilepsy treatments primarily aim to reduce seizure likelihood rather than address the underlying disease process. Sodium channel blockers (SCBs) may effectively treat epilepsy caused by SCN2A mutations. The discovery of more epilepsy gene pathogenic factors enhances our understanding of the epileptogenic process and opens the possibility for targeted gene therapy ^[5]. The ASO drug elsunersen (PRAX-222), developed by Praxis Precision Medicines, has received Priority Medicines (PRIME) certification from the European Medicines Agency (EMA) for treating SCN2A gain-of-function (GoF) developmental epileptic encephalopathy (DEE) ^[6-9]. Considering the genetic differences between animals and humans, humanizing mouse genes can expedite the clinical stages of these treatments. This strain is a humanized model of the mouse Scn2a gene, useful for epilepsy research. The homozygous huSCN2A 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 and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.

The activin A receptor type 1C (ACVR1C), also known as activin receptor-like kinase 7 (ALK7), is a crucial type I serine/threonine kinase receptor belonging to the transforming growth factor-β (TGF-β) superfamily signaling pathway. Upon binding ligands such as activin AB, activin B, and NODAL, ACVR1C initiates intracellular signaling cascades by phosphorylating downstream SMAD2 and SMAD3 transcription factors, thereby regulating diverse cellular processes including cell differentiation, proliferation, apoptosis, and metabolic homeostasis ^[1]. ACVR1C exhibits a broad expression profile across various tissues, with notable enrichment in adipose tissue, pancreas, heart, and specific brain regions, suggesting its pleiotropic roles in maintaining tissue function ^[2]. Dysregulation of ACVR1C signaling has been implicated in a range of metabolic disorders, including obesity and type 2 diabetes, as well as in the pathogenesis of certain cancers like retinoblastoma, highlighting its significance as a potential therapeutic target for these conditions ^[3]. The huALK7(ACVR1C) mouse is a humanized model constructed through gene-editing technology, in which the sequence from the 5'UTR to the downstream of the 3'UTR of the mouse Acvr1c gene is replaced with the sequence from the 5'UTR to the downstream of the 3'UTR of the human ACVR1C gene. This model can be used for the research on the pathological mechanisms and treatment methods of metabolic diseases such as obesity and type 2 diabetes (T2D) and malignant tumors such as retinoblastoma, as well as the development of ACVR1C-targeted drugs.

Cannabinoid receptor 1 (CNR1) is a member of the G protein-coupled receptor (GPCR) superfamily, predominantly expressed in the central nervous system regions, including the cerebral cortex, hippocampus, basal ganglia, and cerebellum ^[1]. CNR1 binds to endocannabinoids and mediates retrograde trans-synaptic signaling, modulating the release of neurotransmitters such as GABA and glutamate, thereby regulating diverse physiological processes including appetite, energy metabolism, mood, cognition, and addiction ^[2]. Studies have shown that CNR1 dysfunction is closely associated with obesity, type 2 diabetes (T2D), schizophrenia, and substance dependence, establishing CNR1 as an important drug target for metabolic and neuropsychiatric diseases ^[3]. The huCNR1(2) mouse is a humanized model generated via gene editing. The sequences from the start codon to the 3'UTR of the endogenous mouse Cnr1 gene were replaced with the sequences from the start codon to the 3'UTR of the human CNR1 gene. This model is suitable for studying the mechanisms of metabolic and neuropsychiatric disorders, as well as for the screening, development, and preclinical in vivo evaluation of CNR1-targeted candidate drugs.

CD8a (CD8 antigen, alpha chain) is a type I transmembrane glycoprotein primarily expressed on the surface of cytotoxic T lymphocytes (CTLs). As a member of the immunoglobulin superfamily, it serves as a critical co-receptor in T cell-mediated adaptive immune responses ^[1]. CD8a forms heterodimers (CD8αβ) with CD8b or homodimers (CD8αα) via disulfide bonds, and together with the T cell receptor (TCR), recognizes antigenic peptides presented by MHC class I molecules on antigen-presenting cells (APCs). Through its cytoplasmic domain, CD8a recruits the LCK tyrosine kinase, initiating the T cell activation signaling cascade and promoting CTL proliferation, differentiation, and cytotoxic function ^[2-3]. The CD8A gene is located on human chromosome 2 (2p12), and the CD8α chain it encodes plays a central role in anti-tumor immune surveillance, antiviral immunity, and autoimmune disease regulation. Targeting the CD8 co-receptor signaling pathway or CD8+ T cell-based adoptive cell therapies (e.g., CAR-T, TCR-T) have become important strategies in tumor immunotherapy ^[4-5]. The huCD8A mouse is a humanized model generated through gene editing technology, in which the endogenous extracellular domain of mouse Cd8a was replaced with the human CD8A extracellular domain, while the murine signal peptide, helical and cytoplasmic regions were retained. This model is suitable for in vivo efficacy and safety evaluation of antibody‑based therapeutics and CAR‑T/TCR‑T cell therapies targeting human CD8A, as well as for studying the functional mechanisms of CD8+ T cells in tumor immunity and infectious diseases.

The SLC3A2 gene (Solute Carrier Family 3 Member 2), also known as CD98hc or 4F2hc, is ubiquitously expressed across many tissues and is often upregulated in various cancers, including lung, breast, and colorectal cancer. It encodes the cell-surface, transmembrane heavy chain of a heterodimeric amino acid transporter complex, which is covalently bound via disulfide bonds to a light chain from the SLC7A family (e.g., SLC7A5/LAT1 or SLC7A11/xCT). The primary function of the encoded protein is to act as a chaperone necessary for the light chain's proper plasma membrane localization and stability. The resulting functional complex transports specific essential amino acids; for instance, the SLC3A2/SLC7A5 dimer transports L-type neutral amino acids, while the SLC3A2/SLC7A7 dimer transports dibasic amino acids. This nutrient uptake is crucial for cell growth and metabolic reprogramming ^[1]. Beyond its transport role, SLC3A2 independently modulates integrin-dependent signaling pathways, affecting processes like cell spreading, adhesion, migration, and proliferation, which links it closely to cancer progression ^[2]. Cellular tissues with notable expression include trophoblasts (placenta), kidney proximal tubular cells, glandular cells (breast), Sertoli cells (testis), and various immune cells. SLC3A2 is primarily associated with cancer, where it acts as an oncoprotein and prognostic marker. It is also involved in specific cell death pathways like disulfidptosis ^[3]. Genetic associations have also been suggested between the SLC3A2 locus and conditions like schizophrenia, vitiligo, and Ulcerative Colitis, highlighting its broader role in cellular homeostasis ^[4]. huCD98HC(SLC3A2) mouse is a humanized model generated using gene editing technology, in which the mouse Slc3a2 endogenous extracellular domain is replaced with the human SLC3A2 extracellular domain. The murine cytoplasmic domain and transmembrane domain are preserved. This model can be used for research related to cancer, amino acid transport and metabolic intervention, immune regulation and autoimmunity, as well as the development of SLC3A2-targeted drugs.

Interleukin-5 (IL-5) is a cytokine secreted by Th2 CD4+ T cells, mast cells, and type 2 innate lymphoid cells (ILC2s). It plays a pivotal role in regulating the proliferation, differentiation, activation, and survival of eosinophils ^[1]. The IL5 gene is located within the 5q31 region of human chromosome 5, clustered alongside other Th2 cytokine genes such as IL4 and IL13, and is co-regulated by transcription factors including GATA3 ^[2]. By binding to the IL-5 receptor alpha chain (IL-5Rα), IL-5 activates signaling pathways like JAK2-STAT5, thereby modulating eosinophil-associated immune responses ^[1-2]. Aberrant IL-5 expression is closely linked to various eosinophil-related disorders, including asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), hypereosinophilic syndrome, and allergic rhinitis, making the IL-5/IL-5Rα axis a prominent therapeutic target. Consequently, several antibody drugs targeting IL-5 or IL-5Rα, such as Mepolizumab and Benralizumab, have been approved or are currently under clinical investigation ^[3-4]. The huIL5 mouse is a humanized model generated by replacing the mouse Il5 gene sequence (from the start codon to the stop codon) with the corresponding human IL5 sequence via in situ substitution. This model is highly valuable for studying eosinophilic diseases (e.g., asthma, CRSwNP, and hypereosinophilic syndrome), allergic inflammatory immune regulation, and Th2 immune responses. Furthermore, it serves as a robust platform for the development of IL-5-targeted therapeutics.

The IL31 gene encodes Interleukin-31, a pleiotropic inflammatory cytokine primarily produced by activated T helper 2 (Th2) cells, but also by mast cells, macrophages, and dendritic cells. It functions by binding to a heterodimeric receptor complex composed of Interleukin-31 receptor alpha (IL-31RA) and Oncostatin M Receptor (OSMR), which are constitutively expressed on various cell types, including epithelial cells, keratinocytes, monocytes, and subsets of neurons in dorsal root ganglia ^[1-2]. This binding activates intracellular signaling pathways such as JAK/STAT, PI3K/AKT, and MAPK, leading to functions in regulating hematopoiesis, immune responses, and the induction of chemokines and pro-inflammatory cytokines ^[1]. IL-31 is strongly associated with pruritic (itchy) skin diseases like atopic dermatitis (eczema), allergic contact dermatitis, prurigo nodularis, and bullous pemphigoid, playing a key role in the sensation of itch ^[3]. It has also been implicated in other conditions such as asthma, allergic rhinitis, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, vitiligo, and various cancers (e.g., follicular lymphoma, endometrial cancer, hepatocellular carcinoma) ^[4]. The B6-hIL31 mouse is a humanized model, constructed by replacing the coding sequences of the endogenous mouse Il31 gene with the coding sequences of the human IL31 gene. B6-hIL31 mice can be used for research into the pathogenesis of various inflammatory diseases and cancers. They are also useful for the screening, development, and safety evaluation of IL31-targeted drugs.