The MYC oncogene family comprises regulatory genes and proto-oncogenes that encode transcription factors, involved in various cellular processes such as the cell cycle, apoptosis, DNA repair, and metabolism. Members include c-Myc (MYC), l-Myc (MYCL), and n-Myc (MYCN). c-Myc (MYC) is a basic helix-loop-helix leucine zipper (bHLHZip) transcription factor, which forms heterodimers with Max protein to bind DNA and regulate the expression of approximately 15% of genes, thereby participating in key cellular processes such as cell proliferation, apoptosis, DNA repair, and metabolism. In many cancers, c-Myc is overexpressed, leading to uncontrolled cell proliferation and tumor growth, such as in Burkitt's lymphoma where c-Myc gene rearrangement is common. Dysregulation of the MYC oncogene plays a crucial role in tumorigenesis, predominantly through transcriptional dysregulation resulting in overexpression of c-Myc protein. Alb-Cre+/MYC+ mice are generated by crossing H11-CAG-LSL-hMYC-IRES-EGFP mice (Catalog Number: C001338), which conditionally express the human c-Myc oncogene, with Alb-Cre mice that express Cre recombinase specifically in hepatocytes under the control of the Alb promoter. The Cre-mediated recombination results in the deletion of the transcriptional stop sequence (Loxp-Stop-Loxp, LSL) in H11-CAG-LSL-hMYC-IRES-EGFP mice, leading to overexpression of the MYC oncogene in the liver and subsequent carcinogenesis. This model, therefore, spontaneously develops liver cancer with an early onset.

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 B6-hTFRC (CDS) mouse model was generated by inserting the human TFRC gene sequence into the mouse Tfrc gene locus using gene-editing technology. To minimize interference from mouse gene sequences or proteins, part of the mouse Tfrc gene sequence was knocked out, resulting in a model expressing only the human TFR1 protein. This model is valuable for studying iron metabolism disorders, neurodegenerative diseases, and tumor development, supporting the development of TFR1-targeted therapeutics and preclinical pharmacological evaluations.

Calcitonin-related polypeptide alpha (CALCA) is a protein-encoded gene, also known as CALC1, CGRP, or CGRP-α. Multiple genetic factors and epigenetic modifications regulate CALCA gene expression, and it forms peptide hormones calcitonin (CT), α-isoform of calcitonin gene-related peptide (CGRP), and katacalcin through tissue-specific RNA alternative splicing and non-active precursor protein cleavage in transcription and translation. Calcitonin is synthesized and secreted by thyroid parafollicular cells, mainly involved in regulating calcium levels and phosphorus metabolism in bones and kidneys. It can reduce the concentration of calcium and phosphorus in the plasma and inhibit the absorption of calcium and phosphorus. CGRP mainly acts as a vasodilator and antimicrobial peptide, which can cause dilatation of coronary arteries, cerebral vessels, and systemic vessels, and help to regulate blood pressure. CGRP is also widely distributed in the pain pathways of the peripheral and central nervous system (CNS) of the human body, and its receptors are also expressed in the pain pathways. CGRP participates in the transmission of pain signals from the periphery to the CNS and plays a key role in pain regulation, which is related to the pathogenesis of a variety of pain diseases and related syndromes, including somatic pain, visceral pain, neuropathic pain, inflammatory pain, and migraine. Katacalcin mainly exists as a peptide that can effectively lower plasma calcium, and its effect of lowering serum calcium levels is almost the same as that of calcitonin. CALCA gene polymorphism is associated with a variety of diseases, including reflex sympathetic dystrophy syndrome, complex regional pain syndrome, ischemic stroke, Parkinson's disease, ovarian cancer, bone mineral density, migraine, schizophrenia, bipolar disorder, and primary hypertension ^[1-5]. CALCA is a potential target for new therapies for a variety of diseases. Currently, various CALCA antagonists are being developed for the treatment of migraine and primary hypertension, and research on targeting CALCA for diseases such as Alzheimer's disease and Parkinson's disease is also ongoing ^[6-7]. This strain is a humanized mouse model of the Calca gene. Using gene editing technology, the base sequence of the mouse Calca gene from the start codon to the 3’UTR region was replaced by the corresponding sequence in the human CALCA gene, while the 5’UTR region of the mouse Calca gene was retained. Homozygous B6-hCALCA mice are viable and fertile and can be used to study the mechanisms of various physiological and pathological processes such as blood pressure regulation, cell proliferation, cell apoptosis, vascular biology, physiological bone marrow production, inflammation, tumor growth, and research on CALCA-targeted migraine drugs and therapies.

Neonatal Fc receptor (FcRn) is a cell surface receptor protein that binds to the Fc region of IgG antibodies. It is structurally similar to MHC class I molecules and is composed of an α-chain and β2-microglobulin (β2M). The α-chain of the FcRn receptor is encoded by the Fcγ receptor and transporter (FCGRT) gene, while β2-microglobulin is encoded by the β-2-microglobulin (B2M) gene. FcRn is expressed widely on epithelial cells, endothelial cells, and hematopoietic cells, and is found in various tissues and organs, including the intestine, placenta, kidney, and liver ^[1-2]. IgG antibodies are the most abundant immunoglobulins in human serum (about 75%), and play an important role in the immune response by defending against pathogens and toxins. Compared to other immunoglobulins, IgG has a high circulating level, a longer half-life, and the ability to be transferred from mother to offspring. These properties are closely related to its interaction with FcRn. FcRn binds to the Fc region of IgG, preventing IgG molecules from being degraded by lysosomes. This prolongs the in vivo half-life of IgG and is involved in the transport, maintenance, and distribution metabolism of IgG. In addition, the specific transport process of IgG from the mother to the fetus to provide the fetus with short-term passive immunity is also mediated by FcRn ^[1-2]. In addition to its protective role, IgG autoantibodies are also associated with many pathological conditions. Therefore, novel FcRn blocking therapies are an effective strategy to reduce the circulating levels of pathogenic IgG autoantibodies and to reduce IgG-mediated diseases. In addition, many drugs also utilize FcRn's protective mechanism for IgG by fusing or conjugating with the Fc portion of IgG to prolong its serum half-life and improve its pharmacokinetics. The FCGRT gene encodes the α-chain of the FcRn protein, and its homologous genes are present in most mammals. The ALB gene encodes albumin, mainly produced in the liver, and is the most abundant protein in human plasma, accounting for 60% to 65% of total plasma protein. The proprotein encoded by ALB is processed to produce a functional protein, and the EPI-X4 peptide derived from this protein is an endogenous inhibitor of the CXCR4 chemokine receptor. Albumin plays a role in regulating plasma colloid osmotic pressure, helping to maintain blood circulation and isolating and transporting many metabolites within the body, especially insoluble hydrophobic metabolites ^[3]. Human Serum Albumin (HSA) is an important carrier protein involved in the transport of a variety of endogenous molecules, including hormones, fatty acids, and metabolic products, as well as exogenous drugs. As a natural carrier protein, HSA has multiple ligand binding sites and a plasma half-life of up to 19 days, making it a promising drug carrier. Several HSA-based drug delivery systems have been approved for clinical trials ^[4-5]. Albumin is also the primary transporter of zinc, calcium, and magnesium in plasma, binding approximately 80% of all plasma zinc and about 45% of circulating calcium and magnesium, with an affinity ranking order of zinc > calcium > magnesium. Additionally, albumin exhibits broad substrate-specific esterase-like activity, with enzymatic properties. It can also bind to the bacterial siderophore enterobactin, inhibiting enterobactin-mediated uptake of iron from transferrin by Escherichia coli, thus limiting iron availability and intestinal bacterial growth ^[6]. Diseases related to the ALB gene include hyperthyroxinemia, familial dysalbuminemic hyperthyroxinemia, and analbuminemia ^[7]. The B6-hFcRn (Extra) /hALB (HSA) mice were obtained by crossbreeding B6N-hFCRN (Extra) humanized mice (Catalog Number: C001701) with B6-hALB (HSA) humanized mice (Catalog Number: C001492). In this model, the gene sequence encoding the extracellular domain of the FCRN protein in the mouse Fcgrt gene was replaced with the corresponding gene sequence from the human FCGRT gene, which is the binding site for the FCRN and IgG antibody Fc structure. Additionally, the mouse Alb gene sequence (including UTR regions) was replaced in situ with the human ALB gene sequence. Therefore, the B6-hFcRn (Extra) /hALB (HSA) mice can be used for in vivo studies of human IgG antibodies, drug development using human serum albumin (HSA) as a carrier, as well as for pharmacodynamic and pharmacokinetic studies.

The DPP4 gene (CD26) encodes dipeptidyl peptidase 4, an intrinsic type II transmembrane glycoprotein and a serine exopeptidase involved in glucose and insulin metabolism and immune regulation. The DPP4 protein is a functional receptor for the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The spike protein of MERS-CoV binds to DPP4, mediating the virus's attachment to host cells and promoting virus-cell fusion, thereby initiating infection ^[1-2]. Studies have found that the DPP4 protein may interact with the S1 domain of the spike glycoprotein of COVID-19, aiding in enhancing the transmission efficiency of viral particles ^[3]. Experimental evidence has shown that hDPP4 transgenic mice infected with MERS-CoV experience high mortality and severe pneumonia ^[4]. These mice infected with Manis javanica HKU4-related coronavirus (MjHKU4r-CoV-1) develop mild to moderate pulmonary histological damage ^[5]. Thus, gene-edited mice expressing human DPP4 protein are important tools for studying coronavirus infections. Additionally, DPP4 expression is severely dysregulated in diseases such as inflammation, cancer, obesity, and diabetes. DPP4 is highly expressed in the intestine, where it selectively cleaves N-terminal dipeptides from various substrates, including incretins, to inactivate multiple bioactive peptides. Since incretins like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are crucial for regulating postprandial insulin secretion, inhibiting DPP4 to elevate endogenous GLP-1 and GIP levels to increase insulin levels has become an important treatment method for type 2 diabetes (T2D) ^[6]. The B6-hDPP4(line 1) mouse is a humanized model constructed by gene editing technology to replace a partial region of the mouse Dpp4 gene with the human DPP4 gene CDS sequence. This model can be used to study the infection mechanisms of viruses such as MERS-CoV and COVID-19, as well as to develop related virus vaccines. Additionally, this model can be utilized to develop DPP4 inhibitor therapies. Additionally, Cyagen Biosciences has developed B6-hDPP4(line 2) mice (Catalog ID: I001188) on the C57BL/6JCya background strain and BALB/c-hDPP4(line 2) mice (Catalog ID: I001189) on the BALB/cAnCya background strain. These two models replace the mouse Dpp4 gene p.S29 to part of intron 2 with the "Human DPP4 CDS-rBG pA" expression cassette, meeting the experimental needs for different strain backgrounds.

The DPP4 gene (CD26) encodes dipeptidyl peptidase 4, an intrinsic type II transmembrane glycoprotein and a serine exopeptidase involved in glucose and insulin metabolism and immune regulation. The DPP4 protein is a functional receptor for the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The spike protein of MERS-CoV binds to DPP4, mediating the virus's attachment to host cells and promoting virus-cell fusion, thereby initiating infection ^[1-2]. Studies have found that the DPP4 protein may interact with the S1 domain of the spike glycoprotein of COVID-19, aiding in enhancing the transmission efficiency of viral particles ^[3]. Experimental evidence has shown that hDPP4 transgenic mice infected with MERS-CoV experience high mortality and severe pneumonia ^[4]. These mice infected with Manis javanica HKU4-related coronavirus (MjHKU4r-CoV-1) develop mild to moderate pulmonary histological damage ^[5]. Thus, gene-edited mice expressing human DPP4 protein are important tools for studying coronavirus infections. Additionally, DPP4 expression is severely dysregulated in diseases such as inflammation, cancer, obesity, and diabetes. DPP4 is highly expressed in the intestine, where it selectively cleaves N-terminal dipeptides from various substrates, including incretins, to inactivate multiple bioactive peptides. Since incretins like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are crucial for regulating postprandial insulin secretion, inhibiting DPP4 to elevate endogenous GLP-1 and GIP levels to increase insulin levels has become an important treatment method for type 2 diabetes (T2D) ^[6]. The B6-hDPP4(line 2) mouse is a humanized model constructed by gene editing technology to replace a partial region of the mouse Dpp4 gene with the human DPP4 gene CDS sequence. This model can be used to study the infection mechanisms of viruses such as MERS-CoV and COVID-19, as well as to develop related virus vaccines. Additionally, this model can be utilized to develop DPP4 inhibitor therapies. Similar models include the B6-hDPP4(line 1) mouse (Catalog ID: I001187), constructed on the C57BL/6NCya background strain, which replaces the sequence of the mouse Dpp4 gene with the human DPP4 gene CDS sequence, and the BALB/c-hDPP4(line 2) mouse (Catalog ID: I001189), constructed on the BALB/cAnCya background strain. These models meet the experimental needs of different strain backgrounds.

The DPP4 gene (CD26) encodes dipeptidyl peptidase 4, an intrinsic type II transmembrane glycoprotein and a serine exopeptidase involved in glucose and insulin metabolism and immune regulation. The DPP4 protein is a functional receptor for the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The spike protein of MERS-CoV binds to DPP4, mediating the virus's attachment to host cells and promoting virus-cell fusion, thereby initiating infection ^[1-2]. Studies have found that the DPP4 protein may interact with the S1 domain of the spike glycoprotein of COVID-19, aiding in enhancing the transmission efficiency of viral particles ^[3]. Experimental evidence has shown that hDPP4 transgenic mice infected with MERS-CoV experience high mortality and severe pneumonia ^[4]. These mice infected with Manis javanica HKU4-related coronavirus (MjHKU4r-CoV-1) develop mild to moderate pulmonary histological damage ^[5]. Thus, gene-edited mice expressing human DPP4 protein are important tools for studying coronavirus infections. Additionally, DPP4 expression is severely dysregulated in diseases such as inflammation, cancer, obesity, and diabetes. DPP4 is highly expressed in the intestine, where it selectively cleaves N-terminal dipeptides from various substrates, including incretins, to inactivate multiple bioactive peptides. Since incretins like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are crucial for regulating postprandial insulin secretion, inhibiting DPP4 to elevate endogenous GLP-1 and GIP levels to increase insulin levels has become an important treatment method for type 2 diabetes (T2D) ^[6]. The BALB/c-hDPP4(line 2) mouse is a humanized model constructed by gene editing technology to replace a partial region of the mouse Dpp4 gene with the human DPP4 gene CDS sequence. This model can be used to study the infection mechanisms of viruses such as MERS-CoV and COVID-19, as well as to develop related virus vaccines. Additionally, this model can be utilized to develop DPP4 inhibitor therapies. Similar models include the B6-hDPP4(line 1) mouse (Catalog ID: I001187), constructed on the C57BL/6NCya background strain, which replaces the sequence of the mouse Dpp4 gene with the human DPP4 gene CDS sequence, and the B6-hDPP4(line 2) mouse (Catalog ID: I001188), constructed on the C57BL/6JCya background strain. These models meet the experimental needs of different strain backgrounds.

The ALB gene encodes albumin, mainly produced in the liver, and is the most abundant protein in human plasma, accounting for 60% to 65% of total plasma protein. The proprotein encoded by ALB is processed to produce a functional protein, and the EPI-X4 peptide derived from this protein is an endogenous inhibitor of the CXCR4 chemokine receptor. Albumin plays a role in regulating plasma colloid osmotic pressure, helping to maintain blood circulation and isolating and transporting many metabolites within the body, especially insoluble hydrophobic metabolites ^[1]. Human Serum Albumin (HSA) is an important carrier protein involved in the transport of a variety of endogenous molecules, including hormones, fatty acids, and metabolic products, as well as exogenous drugs. As a natural carrier protein, HSA has multiple ligand binding sites and a plasma half-life of up to 19 days, making it a promising drug carrier. Several HSA-based drug delivery systems have been approved for clinical trials ^[2-3]. In addition, albumin is also the main transporter of zinc, calcium, and magnesium in plasma, binding approximately 80% of all plasma zinc and approximately 45% of circulating calcium and magnesium, with an affinity ranking of zinc > calcium > magnesium ^[4]. Diseases associated with the ALB gene include hyperthyroxinemia, familial serum albumin abnormality, and analbuminemia ^[5]. 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 ^[6]. 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 ^[7]. 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 ^[6]. 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 ^[8]. B6-hALB/hTFRC mice are a dual gene humanized model of Alb and Tfrc, obtained by crossing B6-hALB (HSA) mice (Catalog number: C001492) with B6-hTFRC (CDS) mice (Catalog number: C001584). This model can be used for the development of ALB/TFRC-targeted therapeutic drugs, as well as for the research on drug development using human serum albumin (HSA) as a carrier or drug delivery across the blood-brain barrier (BBB), and for in vivo pharmacodynamic and pharmacokinetic studies.

The RAMP1 gene (Receptor Activity Modifying Protein 1) encodes a single-transmembrane-domain accessory protein that is crucial for the proper function of certain G protein-coupled receptors (GPCRs) ^[1]. Its primary role is to chaperone the calcitonin receptor-like receptor (CRLR) to the cell surface and to determine its ligand specificity. When co-expressed with CRLR, RAMP1 forms the functional receptor for calcitonin gene-related peptide (CGRP), a potent vasodilator. RAMP1 is involved in the terminal glycosylation, maturation, and presentation of the CGRP receptor ^[2]. Gene expression of RAMP1 is observed in a wide range of cellular tissues, including those in the brain (hypothalamus, brainstem, cortex), adrenal gland, alimentary system, bone, reproductive system, various muscle tissues (psoas muscle, skeletal muscle, muscle of trunk), and immune cells like natural killer cells, T-cells, B-cells, and CD14-positive monocytes ^[3]. Dysregulation of RAMP1 is associated with several diseases, most notably migraine, but also conditions like essential hypertension, cerebral infarction, acute lung injury, chronic inflammation, certain cancers (e.g., prostate cancer, gastric cancer), and metabolic disorders ^[3-4]. The B6-hRAMP1 mouse is a humanized model, constructed by replacing the partial coding sequences of mouse Ramp1 exon 1 with the Kozak-human RAMP1 CDS-3'UTR of mouse Ramp1-WPRE-BGH pA cassette. B6-hRAMP1 mice can be used for research into the pathogenesis of migraine, essential hypertension, cerebral infarction, acute lung injury, chronic inflammation, certain cancers, and metabolic disorders. They are also useful for the screening, development, and safety evaluation of RAMP1-targeted drugs.

The UBE3A gene encodes ubiquitin-protein ligase E3A, a critical enzyme in the ubiquitin-proteasome degradation system responsible for catalyzing substrate ubiquitination and regulating proteasomal clearance. This process is indispensable for maintaining proteostasis, particularly in neurons, where UBE3A governs synaptic plasticity, neural signaling, and neurodevelopment by modulating the levels of specific substrates. As an imprinted gene, UBE3A exhibits parent-of-origin-specific expression in brain neurons. The paternal allele is epigenetically silenced via cis-acting repression by a long noncoding antisense transcript (UBE3A-ATS) ^[1]. Consequently, only the maternal UBE3A allele is functionally active in neuronal populations. Loss of maternal UBE3A function disrupts ubiquitin-mediated proteolysis, leading to aberrant accumulation of neurodevelopmental regulators and subsequent dysregulation of synaptic maturation and circuit formation. These molecular deficits underlie the pathogenesis of Angelman syndrome (AS), a severe neurogenetic disorder. Patients with Angelman Syndrome commonly exhibit severe motor and intellectual developmental delays, ataxia, hypotonia, epilepsy, speech impairment, and distinctive facial features ^[2]. 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 ^[3]. 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 ^[4]. 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 ^[3]. 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 ^[5]. The B6-hTFRC/Ube3a KO mice are generated by crossing B6-hTFRC(CDS) mice with Ube3a KO mice. These mice can be used for studying the pathogenesis of Angelman syndrome (AS), developing related therapeutic approaches, and conducting preclinical research on TFRC-targeted drugs.