The Insulin-like Growth Factor 1 Receptor (IGF-1R), encoded by the IGF1R gene, is a receptor tyrosine kinase expressed in most tissues and cells. Its expression is developmentally regulated and influenced by nutrition, hormones, and intracellular factors, with high expression during growth and development, declining in adulthood ^[1]. The IGF1R protein is a heterotetramer (α2β2) of α and β subunits derived from a precursor protein, forming transmembrane αβ chains. The α chain is located extracellularly, while the β chain spans the cell membrane and is responsible for intracellular signal transduction after ligand stimulation. IGF1R binds Insulin-like Growth Factor-1 (IGF-1) with high affinity, mediating IGF-1's growth-promoting effects and regulating cell growth, differentiation, survival, and metabolism ^[1-4], and IGF1R defects are linked to growth retardation and diabetes ^[2-4]. Furthermore, IGF1R overexpression in tumors promotes proliferation, invasion, and metastasis, making it a cancer therapy target ^[3]. In thyroid eye disease (TED), an autoimmune disorder, activating IGF1R antibodies can be detected. IGF1R is overexpressed in T cells, B cells, and orbital fibroblasts of patients, forming a signal transduction complex with the thyroid-stimulating hormone receptor, thereby enhancing the effect of thyroid-stimulating hormone ^[5]. Therefore, targeting IGF1R to inhibit thyroid-stimulating hormone action is a therapeutic strategy for TED, improving exophthalmos ^[6]. hIGF1R(BALB/c) mice are humanized models generated using gene editing technology by integrating the protein-coding sequence (CDS) encoding the extracellular domain of human IGF1R protein and the intracellular domain of mouse IGF1R protein into the mouse Igf1r gene locus, while retaining the endogenous gene sequence encoding the signal peptide of mouse IGF1R protein. Homozygous hIGF1R(BALB/c) mice are viable and fertile, and can be used for studying the pathological mechanisms and treatments of growth retardation, diabetes, and cancer, as well as for screening, developing, and preclinical efficacy and safety evaluation of IGF1R-targeted drugs.

The Insulin-like Growth Factor 1 Receptor (IGF-1R), encoded by the IGF1R gene, is a receptor tyrosine kinase expressed in most tissues and cells. Its expression is developmentally regulated and influenced by nutrition, hormones, and intracellular factors, with high expression during growth and development, declining in adulthood ^[1]. The IGF1R protein is a heterotetramer (α2β2) of α and β subunits derived from a precursor protein, forming transmembrane αβ chains. The α chain is located extracellularly, while the β chain spans the cell membrane and is responsible for intracellular signal transduction after ligand stimulation. IGF1R binds Insulin-like Growth Factor-1 (IGF-1) with high affinity, mediating IGF-1's growth-promoting effects and regulating cell growth, differentiation, survival, and metabolism ^[1-4], and IGF1R defects are linked to growth retardation and diabetes ^[2-4]. Furthermore, IGF1R overexpression in tumors promotes proliferation, invasion, and metastasis, making it a cancer therapy target ^[3]. In thyroid eye disease (TED), an autoimmune disorder, activating IGF1R antibodies can be detected. IGF1R is overexpressed in T cells, B cells, and orbital fibroblasts of patients, forming a signal transduction complex with the thyroid-stimulating hormone receptor, thereby enhancing the effect of thyroid-stimulating hormone ^[5]. Therefore, targeting IGF1R to inhibit thyroid-stimulating hormone action is a therapeutic strategy for TED, improving exophthalmos ^[6]. hIGF1R mice are humanized models generated using gene editing technology by integrating the protein-coding sequence (CDS) encoding the extracellular domain of the human IGF1R protein and the intracellular domain of the mouse IGF1R protein into the mouse Igf1r gene locus, while retaining the endogenous gene sequence encoding the signal peptide of mouse IGF1R protein. Homozygous hIGF1R mice are viable and fertile, and can be used for studying the pathological mechanisms and treatments of growth retardation, diabetes, and cancer, as well as for screening, developing, and preclinical efficacy and safety evaluation of IGF1R-targeted drugs.

For the Kl model, the TGA stop codon will be replaced by P2A-Cre. A synonymous mutation p.R894=(CGG to CGC) and an additional mutation c.*3C>G in 3'UTR will also be introduced to prevent the binding and re-cutting of the sequence.

The ADIPOQ gene-encoded adiponectin is a protein hormone produced exclusively by adipocytes (fat cells). It is transported through the bloodstream to muscle and liver cells. Adiponectin regulates various pathways related to fat storage and metabolism, including the modulation of blood glucose levels, fatty acid breakdown, brown adipocyte differentiation, and negative regulation of gluconeogenesis. By increasing insulin sensitivity and promoting fatty acid breakdown, adiponectin plays a crucial role in regulating glucose and fat metabolism. Additionally, it exhibits direct anti-diabetic, anti-atherosclerotic, and anti-inflammatory activities ^[1-2]. The mutation of the ADIPOQ gene is associated with adiponectin deficiency syndrome. Although the ADIPOQ gene is primarily expressed in adipose tissue, adiponectin is not only present in adipose tissue but is also widely distributed in various organs and tissues, including muscle, liver, intestines, male reproductive glands, and the brain ^[3-4]. The Adipoq-iCre mice are constructed by inserting a codon-improved Cre recombinase (iCre) element into the endogenous Adipoq gene of mice. The expression pattern of iCre recombinase is similar to the endogenous gene. When this strain is crossed with mice containing loxP sites, sequence recombination mediated by the Cre recombinase between loxP sites can occur in the white adipose tissue (WAT) and brown adipose tissue (BAT) of its offspring.

The ALB gene encodes the most abundant protein in human blood, which functions to regulate plasma colloid osmotic pressure and as a carrier protein for a variety of endogenous molecules, including hormones, fatty acids, and metabolites, as well as exogenous drugs. In addition, the protein exhibits esterase-like activity and has broad substrate specificity. The peptide EPI-X4, derived from this protein, is an endogenous inhibitor of the CXCR4 chemokine receptor. This strain carries a mouse Alb gene promoter-driven improved Cre (iCre) expression element insertion. When H11-Alb-iCre mice are crossed with mice containing loxP sites, Cre recombinase-mediated loxP site sequence recombination is induced in liver tissue. The heterozygous H11-Alb-iCre mice developed normally and were fertile.

The CNR1 gene (Cannabinoid Receptor 1) encodes the CB1 receptor, a highly conserved G protein-coupled receptor (GPCR) that serves as the primary molecular target for endocannabinoids like anandamide and exogenous cannabinoids like THC. It is most abundantly expressed in the central nervous system, particularly in the cerebral cortex, hippocampus, basal ganglia, and cerebellum, but is also present in peripheral tissues such as the liver, adipose tissue, and gastrointestinal tract ^[1]. Functionally, CB1 receptors primarily reside on presynaptic terminals where they regulate neurotransmitter release—typically inhibiting the release of GABA or glutamate—to modulate pain, appetite, memory, and emotional processing ^[2]. Dysregulation of CNR1 expression or CB1 signaling is strongly associated with a variety of diseases, including obesity, metabolic syndrome, chronic pain, and neuropsychiatric disorders, such as anxiety, depression, and schizophrenia ^[3-4]. The huCNR1 mouse is a humanized model constructed by using gene-editing technology to replace the sequence from the ATG start codon to the TGA stop codon in the endogenous mouse Cnr1 gene with the sequence from the ATG start codon to the TGA stop codon in the human CNR1 gene. This model can be used for research related to obesity, metabolic syndrome, chronic pain, and neuropsychiatric diseases, such as anxiety, depression, and schizophrenia, as well as for the development of CNR1-targeted drugs.

The APOE3 (Apolipoprotein E epsilon 3) gene represents the most prevalent isoform within the human population and is typically categorized as the functionally "neutral" or wild-type allele. Predominantly expressed in the liver and central nervous system, it is produced by hepatocytes and astrocytes to encode the 299-amino acid Apolipoprotein E glycoprotein ^[1]. This protein serves as a vital ligand for LDL receptors, facilitating the systemic transport and redistribution of cholesterol and triglycerides necessary for membrane stability and neural synaptic repair. While APOE3 generally supports healthy lipid homeostasis, the APOE4 isoform is associated with increased risk of cardiovascular pathologies like atherosclerosis, whereas APOE2 homozygosity (or rare APOE variants) can lead to familial dysbetalipoproteinemia in specific genetic contexts ^[2]. Furthermore, it serves as the baseline for assessing neurodegenerative risk, sitting between the neuroprotective effects of the APOE2 variant and the significantly increased Alzheimer's disease risk associated with APOE4 ^[3]. The huAPOE3 mouse is a humanized model constructed by using gene-editing technology to replace exons 2-4 and part of the flanking sequences of the mouse Apoe gene with the human APOE gene sequences, including exons 2, 3, 4, and some downstream sequence of 3’UTR. This model can be used for research on cardiovascular diseases, such as atherosclerosis, and neurodegenerative diseases, such as Alzheimer's disease (AD), as well as for the development of APOE3-targeted drugs.

The CD22 gene encodes a 140 kDa type I transmembrane glycoprotein that serves as a critical member of the SIGLEC (sialic acid-binding immunoglobulin-like lectin) family. Gene expression is highly restricted to B-lymphocytes, with strong surface expression on mature B cells and high RNA levels in lymphoid tissues such as lymph nodes and spleen ^[1]. The encoded protein functions as a potent inhibitory co-receptor of the B-cell receptor (BCR); upon ligand binding, its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) are phosphorylated, recruiting phosphatases like SHP-1 to attenuate B-cell activation and maintain peripheral tolerance ^[2]. Beyond its regulatory role, CD22 facilitates cell-cell adhesion by recognizing α2,6-linked sialic acids. Due to its restricted expression pattern, CD22 is a major diagnostic marker and therapeutic target in various B-cell malignancies, including hairy cell leukemia, B-cell non-Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL), and it has also been implicated in the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) ^[3]. The huCD22 mouse model was generated by replacing the murine Cd22 sequence from aa.22 through exon 9 with the homologous human CD22 region, all while retaining the mouse signal peptide to facilitate appropriate protein expression. This model is applicable to the study of various autoimmune diseases, including systemic lupus erythematosus (SLE), as well as cancers such as hairy cell leukemia, B-cell non-Hodgkin lymphoma, and acute lymphoblastic leukemia (ALL), and to the development of CD22-targeted therapeutics.

The CIDEB (Cell Death Inducing DFFA Like Effector B) gene encodes a lipid transferase protein that is predominantly expressed in the liver, but also found in significant levels in the small intestine, colon, kidney, and spleen. This protein primarily localizes to the cytosol, perinuclear region of the cytoplasm, and specifically to lipid droplets and the endoplasmic reticulum, where it plays a critical role in lipid metabolism by promoting the fusion of lipid droplets to form larger unilocular droplets, thereby favoring lipid storage and restricting lipolysis ^[1]. CIDEB is also essential for the lipidation and maturation of very-low-density lipoproteins (VLDLs) and chylomicrons, facilitating their transport ^[2]. Beyond lipid metabolism, CIDEB has been implicated in the positive regulation of apoptosis, though its basal expression levels do not typically induce cell death ^[3]. Furthermore, CIDEB influences the replication cycle of hepatitis C virus (HCV) and hepatitis B virus (HBV), acting as a cofactor for HCV entry into hepatocytes ^[4]. Associated diseases include various liver conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV), with rare germline loss-of-function variants in CIDEB demonstrating a protective effect against these liver diseases ^[5]. The huCIDEB(1) mouse is a humanized model, constructed by replacing the sequences from exon 1 to partial intron 2 of mouse Cideb with the Human CIDEB genomic region (exon 1 to exon 5)-rBG pA cassette. huCIDEB(1) mice can be used for research into the pathogenesis of various liver conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV). They are also useful for the screening, development, and safety evaluation of CIDEB-targeted drugs.