The SLC6A19 gene encodes B⁰AT1, a sodium-dependent neutral amino acid transporter. Operating as the primary apical transporter, B⁰AT1 mediates the Na+-dependent (chloride-independent) uptake of most neutral amino acids across epithelial membranes to facilitate intestinal absorption and renal reabsorption ^[1]. This process requires essential accessory proteins: ACE2 in the intestine and collectrin (CLTRN) in the kidney for proper trafficking and functional activity. Primarily expressed in the small intestine and renal proximal tubules—with secondary expression in the pancreas, liver, and brain ependymal cells—B⁰AT1 is vital for systemic amino acid homeostasis. Mutations in this gene result in Hartnup disorder, an autosomal-recessive condition defined by neutral aminoaciduria and tryptophan/niacin deficiencies, which may manifest as pellagra-like rashes, ataxia, or neuropsychiatric issues such as ADHD ^[2]. Interestingly, SLC6A19 is now a therapeutic target. Pharmacological inhibition is being studied to manage phenylketonuria (PKU) by promoting urinary amino acid excretion ^[3]. Furthermore, inhibiting or deleting SLC6A19 mimics the effects of dietary protein restriction, offering metabolic benefits such as improved glucose tolerance, obesity prevention, and elevated levels of FGF21 and GLP-1 ^[4]. The huSLC6A19 mouse model was generated by replacing the sequences from the ATG start codon to 3'UTR of the endogenous mouse Slc6a19 gene with the sequences from the ATG start codon to 3'UTR of the human SLC6A19 gene. This model is applicable to research on metabolic disorders such as Hartnup disease, phenylketonuria (PKU), and obesity, as well as to the screening, development, and safety evaluation of SLC6A19-targeted drugs.

The TCF4 gene encodes Transcription Factor 4, a basic helix-loop-helix (bHLH) transcription factor and a member of the E-protein family. This protein is broadly expressed during nervous system development, demonstrating high expression levels in both embryonic and adult brain tissues, whereas its expression remains relatively low in the majority of normal adult non-neural tissues. As a critical transcriptional regulator, TCF4 modulates downstream gene expression by recognizing and binding to E-box motifs (CANNTG) on DNA. It plays an essential role in neuronal differentiation, synaptogenesis, synaptic plasticity, and the Wnt/β-catenin signaling pathway, and is closely implicated in processes such as cell proliferation, differentiation, and epithelial-mesenchymal transition (EMT) ^[1-2]. Research shows that haploinsufficiency of the TCF4 gene is the primary etiology of Pitt-Hopkins syndrome (PTHS), a disorder primarily characterized clinically by severe intellectual disability, absence of speech, developmental delay, epilepsy, and distinctive facial features ^[3]. Moreover, common variants in the TCF4 gene are significantly correlated with the genetic risk of schizophrenia, autism spectrum disorder (ASD), and other neuropsychiatric conditions ^[4]. Serving as a crucial therapeutic target for transcriptional regulation, TCF4 can be intervened upon via multiple strategies, including small molecule modulators, AAV-mediated gene therapy, antisense oligonucleotides (ASOs), and RNA-based therapies ^[3-5]. Presently, therapeutic approaches targeting TCF4-associated pathways remain largely in preclinical or early-stage development, and are primarily indicated for Pitt-Hopkins syndrome and other neurodevelopmental disorders. With further in-depth research, TCF4 holds promise as a pivotal target for the precision treatment of neurodevelopmental disorders, offering novel directions for mechanistic investigations and therapeutic interventions in related neuropsychiatric diseases. The huTCF4 mouse is a humanized model constructed by gene-editing technology. The region upstream to downstream of mouse Tcf4 was replaced with the region from upstream to downstream of human TCF4. This model can be used for research on Pitt-Hopkins syndrome (PTHS), schizophrenia, autism spectrum disorder (ASD), and other neuropsychiatric disorders, as well as for the development, screening, and preclinical pharmacological and pharmacodynamic evaluation of TCF4-targeted drugs.

The MYBPC3 gene encodes the cardiac isoform of myosin-binding protein C. MYBPC3 is a critical regulator of cardiac contraction, and mutations in this gene are a common cause of hypertrophic cardiomyopathy (HCM). HCM is the most prevalent inherited cardiomyopathy worldwide, following an autosomal dominant inheritance pattern. This condition is marked by unexplained left ventricular hypertrophy, a non-dilated left ventricle with preserved or increased ejection fraction, and myocardial disarray along with interstitial fibrosis. Left ventricular diastolic dysfunction is also common. HCM is a leading cause of sudden cardiac death, particularly in adolescents and young adults ^[1-2]. Research indicates that Mybpc3 homozygous knockout mice exhibit pronounced cardiac hypertrophy and diastolic dysfunction ^[3]. These mice serve as a platform for studying the mechanisms and developing therapeutic approaches for familial hypertrophic cardiomyopathy (FHC). The Mybpc3-KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Mybpc3 gene (the homolog of the human MYBPC3 gene) in mice. This model is used to research the pathogenic mechanisms of hypertrophic cardiomyopathy (HCM) and develop related therapeutic strategies.

Retinitis pigmentosa (RP) is a hereditary retinal disease with a global prevalence of approximately 1:5000-1:3000. RP is highly clinically and genetically heterogeneous, with mutations in the rhodopsin (RHO) gene causing approximately 25% of dominant RP ^[1]. The rhodopsin encoded by the RHO gene is closely associated with visual light transduction and GPCR downstream signals. Rhodopsin is essential for the transmission of light signals in the process of vision formation. Most RHO mutations lead to high levels of rhodopsin expression in photoreceptor cells, causing many mutant proteins to be abnormally located and aggregated in cells. This results in the apoptosis of photoreceptor cells, which cannot perform normal light signal transduction functions. Additionally, mutations in the RHO gene are associated with congenital stationary night blindness (CSNB) ^[2-6]. Mutations in the RHO gene can lead to rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP). In 25% of autosomal dominant inherited RP (adRP) cases, there are over 150 different RHO gene mutations. Notably, the P23H mutation is one of the most prevalent, accounting for 10% of adRP cases ^[2]. Previous studies have shown that mice carrying the heterozygous human RHO P23H mutation exhibit retinopathy and progressive retinal degeneration similar to the patient's disease process, which could be used for visual signaling and retinitis pigmentosa (RP) studies ^[3]. Current gene therapy targeting the RHO gene to treat retinitis pigmentosa includes ASO, CRISPR, and others. Applying fully humanized animal models will promote the further development of RHO-related potential therapies in clinical trials ^[7-11]. This strain is a mouse Rho gene humanized model, in which the endogenous mouse Rho gene and Rho gene promoter are replaced by the human RHO gene carrying a P23H mutation and RHO gene promoter to express human retinal proteins in mice. Therefore, the abnormal protein encoded by the human gene was expressed in mice, resulting in abnormal retinal appearance and function and visual defects in this model. Based on the self-developed technological innovation of TurboKnockout fusion BAC recombination, Cyagen can also provide customized services for different point mutations to meet the needs of a wide range of R&D personnel regarding the pharmacodynamics of retinitis pigmentosa (RP) and other preclinical needs.

Ms4a3 (Membrane spanning 4-domains subfamily A member 3) is a member of the MS4A transmembrane protein family and is primarily expressed in granulocyte-monocyte progenitors (GMPs) and their downstream myeloid cells, including neutrophils, monocytes, eosinophils, and basophils. Studies have shown that Ms4a3 plays important roles in myeloid cell differentiation, hematopoietic development, and immune lineage specification, and has been widely used as a marker gene for myeloid progenitors and their descendant cells. In recent years, Ms4a3-related lineage tracing systems have been applied in studies of the developmental origins of neutrophils and monocyte-macrophage lineages, inflammatory responses, and tissue immune microenvironments. Ms4a3-IRES-iCre mice were generated by knocking an IRES-iCre cassette into the endogenous Ms4a3 locus, enabling the expression of codon-optimized iCre recombinase under the control of endogenous Ms4a3 regulatory elements. When crossed with mice containing loxP sites, Cre-mediated recombination between loxP sites is expected to occur in Ms4a3-positive cells of the offspring.

Scx (Scleraxis) is a basic helix-loop-helix (bHLH) transcription factor that plays critical regulatory roles during the development of tendons, ligaments, heart valves, and certain mesenchymal tissues ^[1-3]. Scx is primarily expressed in tenocytes, ligament cells, and mesenchymal progenitor cells, where it regulates the expression of extracellular matrix-related genes such as Col1a1 and participates in biological processes including tendon formation, tissue remodeling, and injury repair ^[2-4]. Studies have shown that Scx functionally interacts with multiple development- and fibrosis-associated factors, including Smad3, Mkx, Sox9, Runx2, and the Tgfb family, and plays important roles in heart valve development, myocardial fibrosis, and musculoskeletal injury repair ^[3-5]. Previous studies have also demonstrated that aberrant Scx expression may lead to mesoderm developmental abnormalities, impaired tendon formation, and skeletal-related defects ^[5]. Scx-P2A-iCre mice were generated by replacing the endogenous Scx stop codon with a P2A-iCre cassette, enabling the expression of codon-optimized iCre recombinase under the control of endogenous Scx regulatory elements. When crossed with mice containing loxP sites, Cre-mediated recombination between loxP sites is expected to occur in Scx-positive cells of the offspring.

SRY-Box Transcription Factor 9 (SOX9) is a member of the high-mobility group (HMG) superfamily transcription factors encoded by the Sox9 gene. SOX9 is highly expressed in chondrocytes and is also widely expressed in Sertoli cells, genital ridges, kidneys, hearts, and multiple other tissues ^[1-2]. SOX9 is an important master regulatory transcription factor during chondrogenesis and participates in cartilage matrix synthesis and skeletal development through regulating the transcription of cartilage-associated genes, including Col2a1 and Agc1 ^[2-3]. In addition, SOX9 also plays important roles in gonadal development and maintenance of the germ cell microenvironment ^[1,4]. Studies have shown that aberrations in Sox9 are closely associated with skeletal and gonadal developmental disorders, including campomelic dysplasia and sex reversal syndrome. Therefore, SOX9 has been widely used in studies of skeletal development, reproductive development, and regenerative medicine ^[3-4]. Sox9-IRES-CreERT2 mice were generated by knocking a tamoxifen-inducible CreERT2 cassette into the endogenous Sox9 locus. Without tamoxifen, CreERT2 is retained in the cytoplasm; upon induction, it translocates to the nucleus to mediate recombination. When crossed with mice containing loxP sites, Cre-mediated recombination is expected to occur in Sox9-positive cells of the offspring after tamoxifen induction.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disease characterized by accelerated aging and premature death. Patients with HGPS exhibit rapid organ degeneration and physiological decline beginning in early infancy due to gene mutations. The rate of aging in HGPS patients is 5-10 times faster than in healthy individuals. This disease presents with marked hormonal abnormalities and affected children often exhibit stunted growth, baldness, limited joint mobility, and osteoporosis. Other key abnormalities include prominent scalp veins, delayed tooth eruption, impaired sexual maturation, and a low-pitched voice. Most affected children succumb to cardiovascular disease or stroke due to the rapid development of atherosclerosis ^[1]. HGPS is typically caused by a dominant-negative mutation in the LMNA gene. The LMNA gene encodes lamin A/C, a member of the nuclear lamina protein family. This highly conserved protein family forms a network layer attached to the inner nuclear membrane of eukaryotic cell nuclei. Nuclear lamina proteins play essential roles in maintaining cell structure, facilitating mitosis, and ensuring proper chromosome organization ^[2]. Mutations in the LMNA gene can lead to a spectrum of disorders, including neuromuscular diseases, heart disease, and HGPS ^[3]. LMNA-targeted drug development is still in its early stages, with preclinical studies of related drug pipelines ongoing. Gene therapy approaches targeting the LMNA gene have emerged, including antisense oligonucleotide (ASO) drugs and CRISPR gene editing technology. In vivo studies of these therapies have primarily utilized Lmna^G609G/G609G mice as a disease model for efficacy evaluation ^[1-2]. Preclinical research relies heavily on in vivo studies. Nucleic acid-based and CRISPR gene editing-based HGPS therapies target the human LMNA gene. Developing genetically humanized mouse models will accelerate the progression of gene therapy drug pipelines into clinical trials ^[4]. This strain represents a mouse Lmna gene humanized model, in which the mouse Lmna gene is replaced by the human LMNA gene, including the 3'UTR. It can be employed to investigate the pathogenesis of neuromuscular diseases, heart disease, HGPS, and other disorders, as well as for preclinical evaluation of therapeutic drugs. Homozygous huLMNA mice are viable and fertile. Additionally, based on Cyagen's proprietary TurboKnockout fusion BAC recombination technology, hot mutation models can be generated from this strain, and tailored services for specific mutations can be provided to meet the experimental needs in pharmacology and other HGPS-related fields.

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 expressed predominantly (or almost exclusively) in adipose tissue, adiponectin, as a secreted hormone, circulates via the bloodstream and is widely distributed in various tissues and organs, including skeletal muscle, liver, intestine, male reproductive glands, and brain, where it exerts its physiological effects through specific receptors (such as AdipoR1 and AdipoR2) ^[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.