The ABCD1 (ATP-binding cassette subfamily D member 1) gene, located on the X chromosome (Xq28), encodes a peroxisomal transmembrane protein responsible for transporting very long-chain fatty acids (VLCFAs) into peroxisomes for β-oxidation. Widely expressed but particularly prominent in the brain, adrenal glands, and liver, ABCD1 is critical for maintaining lipid homeostasis. Mutations in ABCD1 cause X-linked adrenoleukodystrophy (X-ALD), a neurodegenerative disorder characterized by VLCFA accumulation, demyelination, adrenal insufficiency, and progressive neurological decline. Clinical manifestations vary widely, ranging from asymptomatic carriers to a severe, fatal childhood form. Primarily affecting males (with an estimated incidence of ~1 in 17,000 newborns), X-ALD has been included in newborn screening programs in many U.S. states ^[1-2]. The correlation between specific mutations and symptoms remains unclear, and VLCFA measurement cannot reliably predict disease-specific outcomes such as adrenal insufficiency or neurological decline. Current therapeutic approaches focus on gene repair or mitigating secondary effects like oxidative stress ^[3]. The Abcd1-KO mouse, a gene knockout model generated by deleting exon 2 of the mouse Abcd1 gene (homologous to human ABCD1), serves as a valuable tool for studying the pathogenesis of X-ALD and developing therapeutic interventions.

P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is an ATP-binding cassette transporter that acts as a biological barrier by expelling toxins and foreign substances from cells. P-gp is capable of transporting many structurally and functionally different compounds out of cells ^[1]. However, the mechanism of MDR1 also prevents the uptake of many cancer treatment drugs by cells, leading to multidrug resistance (MDR) ^[2]. In normal organisms, MDR1’s distribution in the blood-brain barrier and blood-placenta barrier prevents exogenous drugs and toxins from entering the central nervous system and placenta of the organism, thereby protecting the organism and enabling it to perform normal physiological functions. In pathological conditions, however, the MDR1 in the blood-brain barrier prevents drugs from entering the central nervous system, and in tumor cells, leads to the development of MDR. The evolution of MDR remains one of the major obstacles to controlling or curing cancer ^[3-4]. In humans, the MDR1 protein is encoded by the ABCB1 gene. In mice, two closely located genes, Abcb1a and Abcb1b, encode the MDR1a and MDR1b subtypes of this protein. Mouse MDR1a and MDR1b have 80% homology with human MDR1. MDR1a and MDR1b have the same function as human MDR1 protein in resisting anticancer drugs. Although mouse MDR1a and MDR1b proteins are distributed in different tissues of the body, their overall distribution is consistent with that of human MDR1 protein ^[5-6]. In summary, the distribution and function of mouse MDR1a and MDR1b are consistent with those of human MDR1. This strain is an MDR1 knockout model, in which the human ABCB1 gene’s homologous genes, Abcb1a and Abcb1b, were knocked out in mice using gene editing technology. This model lacks the expression of MDR1 protein and can be used for research in areas such as blood-brain barrier permeability-related diseases and multidrug resistance of anti-tumor drugs.

Duchenne muscular dystrophy (DMD) is a severe, progressive, and debilitating X-linked disorder characterized by muscle wasting. This condition precipitates difficulties with movement, eventually necessitating assisted ventilation, and often leads to premature death. The primary cause of DMD is mutations in the dystrophin muscular dystrophy (DMD) gene, which encodes the dystrophin protein. These mutations effectively eliminate the production of dystrophin protein in muscle tissues, instigating muscle atrophy and a myriad of complications ^[1]. The absence of dystrophin protein culminates in the disintegration of the dystrophin-associated protein complex (DAPC) within the muscle membrane. This disintegration disrupts the interaction between actin and the extracellular matrix, rendering muscles devoid of dystrophin more susceptible to damage. This susceptibility results in the progressive loss of muscle tissue and function, as well as the development of cardiomyopathy ^[2]. Dmd-Q995*(DBA2;B6) mice carry a c.2983C>T (p.Q995*) mutation in the Dmd gene, which introduces a premature termination codon (PTC) triggering nonsense-mediated mRNA decay (NMD) in eukaryotes. NMD degrades PTC-containing aberrant mRNAs to minimize gene expression errors, as these mRNAs may translate into harmful gain-of-function or dominant-negative proteins disrupting physiological mechanisms. The mutation combined with the murine NMD mechanism leads to the degradation of most Dmd transcripts in Dmd-Q995*(DBA2;B6) mice, with remaining transcripts encoding nonfunctional truncated dystrophin, resulting in loss of dystrophin function ^[3-5]. Additionally, the inherent muscle regeneration dysfunction in the DBA/2 strain exacerbates myopathic phenotypes, including significant muscle atrophy, fibrosis, and pronounced muscle weakness, more accurately mimicking human DMD progression and severity ^[6]. This makes Dmd-Q995*(DBA2;B6) mice, with their lack of functional dystrophin, ideal for modeling Duchenne muscular dystrophy (DMD) and evaluating therapeutic strategies.

Duchenne muscular dystrophy (DMD) is a severe, progressive, and debilitating X-linked disorder characterized by muscle wasting. This condition precipitates difficulties with movement, eventually necessitating assisted ventilation, and often leads to premature death. The primary cause of DMD is mutations in the dystrophin muscular dystrophy (DMD) gene, which encodes the dystrophin protein. These mutations effectively eliminate the production of dystrophin protein in muscle tissues, instigating muscle atrophy and a myriad of complications ^[1]. The absence of dystrophin protein culminates in the disintegration of the dystrophin-associated protein complex (DAPC) within the muscle membrane. This disintegration disrupts the interaction between actin and the extracellular matrix, rendering muscles devoid of dystrophin more susceptible to damage. This susceptibility results in the progressive loss of muscle tissue and function, as well as the development of cardiomyopathy ^[2]. Dmd-Q995* mice carry a c.2983C>T (p.Q995) mutation in the Dmd gene, which results in the production of a premature termination codon (PTC). In eukaryotes, the nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing PTCs to reduce errors in gene expression. These abnormal mRNAs may encode harmful gain-of-function or dominant-negative proteins that can damage normal human physiological mechanisms. In Dmd-Q995* mice, the mutation and the NMD pathway together result in the degradation of most Dmd transcripts. The remaining transcripts can only encode truncated dystrophin proteins that lack normal function, leading to the loss of dystrophin function ^[3-5]. This model, due to the lack of normal dystrophin expression, exhibits a series of muscle disease phenotypes similar to the clinical presentation of Duchenne muscular dystrophy (DMD), and can be used for research on DMD. Homozygous female mice and heterozygous males of this strain are viable and fertile.

The SCN10A gene, which encodes the sodium channel Na(v)1.8, is a susceptibility factor for cardiac conduction block and severe ventricular arrhythmias. Genetic variations in ion channel genes are associated with hereditary arrhythmias, such as Long QT Syndrome, Short QT Syndrome, Brugada Syndrome (BrS), and conduction abnormalities. These variations are also linked to sudden unexplained death (SUD) in young adults and children. Several studies have identified common variants of SCN10A as potential regulators of human PR and QRS durations, with SCN10A being a major susceptibility gene for BrS ^[1-2]. The Nav1.8 protein is expressed in small-diameter sensory neurons of the trigeminal ganglion and dorsal root ganglion (DRG), as well as in some medium- and large-diameter neurons and in layers I and II of the spinal dorsal horn ^[3]. The SCN10A/Nav1.8 voltage-gated sodium channel is crucial in pain management. Studies have shown that Nav1.8 channel inhibitors have the potential to become a new class of effective analgesics suitable for multimodal pain treatment in postoperative patients. Additionally, the low expression of SCN10A in the brain suggests a lower likelihood of adverse effects, including dependency and abuse, within the central nervous system ^[4]. In early 2025, the FDA approved Suzetrigine, a Nav1.8 inhibitor developed by Vertex Pharmaceuticals, marking a breakthrough in the pain management field previously dominated by opioid drugs. As the first non-opioid acute pain medication in two decades, the success of Suzetrigine is a significant milestone. hSCN10A(Nav1.8)(SD) rats are a Scn10a humanized model created by inserting the human SCN10A gene's coding sequence (CDS) and 3'UTR into the rat Scn10a gene. This model can be used for mechanistic studies of acute pain and diabetic peripheral neuropathic pain and the development, screening, and evaluation of analgesic drugs in preclinical research. During the production of this rat strain, scratching behavior was observed after weaning and cage separation, resulting in skin lesions. Trimming the nails at the time of cage separation effectively prevents such skin damage. For long-term prevention, nail trimming should be repeated every 2 weeks.

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal progressive neurodegenerative disease. The disease is caused by the degeneration and death of motor neurons that control skeletal muscles in the central nervous system, leading to gradual muscle weakness and atrophy, and ultimately complete loss of voluntary movement control by the brain ^[1]. Unlike Alzheimer’s disease, ALS does not necessarily affect higher brain functions. On the contrary, late-stage patients can maintain clear thinking and retain memories, personality, and intelligence before the onset of the disease. The known ALS-causing genes include SOD1, ALS2, TARDBP, and FUS, among others. FUS is a multifunctional DNA/RNA-binding protein that is usually localized within the nucleus but can also shuttle between the nucleus and the cytoplasm. The FUS protein plays an important role in processes such as RNA transcription, splicing, and microRNA processing. Mutations in the FUS gene are closely associated with frontotemporal lobar degeneration/dementia (FTLD-FUS) and amyotrophic lateral sclerosis (ALS-FUS). Typically, the histopathological feature of ALS-FUS patients is the mislocalization of the FUS protein to the cytoplasm in spinal cord neurons and glial cells, and the formation of FUS-positive inclusions. However, based on current cases, only a portion of patients exhibit FUS mislocalization, and changes in the nuclear function of FUS mutants can also trigger ALS. Pathological FUS mice can induce neurodegeneration in the absence of cytoplasmic pathological changes or even significant mislocalization, which strongly indicates that the toxic nuclear function of FUS mutants may be a potential pathogenic mechanism. More than 50 FUS gene mutations have been found in patients with familial ALS and sporadic ALS, and the vast majority of them are inherited in an autosomal dominant pattern ^[2]. The mutant FUS protein generated by the R521C mutation in the FUS gene can form a stable complex with the wild-type (WT) FUS protein, interfere with normal protein interactions, cause DNA damage, and exhibit abnormal dendritic and synaptic phenotypes in the mouse brain and spinal cord. There is evidence that FUS-R521C mice have defects in transcription and splicing of genes responsible for regulating dendritic growth and synaptic function ^[3]. The FUS-targeted drugs under research are mainly gene therapy drugs, such as antisense oligonucleotides (ASOs). The ASO drug (ION363) developed by Ionis has entered phase 3 clinical trials. This drug can effectively reduce the abnormal expression of FUS in diseased mice ^[4]. Most gene therapy methods act on human genes. Considering the genetic differences between animals and humans, humanizing the mouse genes will help accelerate the advancement of FUS-targeted gene therapies into the clinical stage. This model is a humanized model. Gene editing technology is used to replace the endogenous mouse Fus gene with a human FUS gene fragment carrying the R521C mutation. huFUS-R521C mice can be used for the research of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration/dementia (FTLD). In addition, based on the technological innovation of TurboKnockout fusion BAC recombination independently developed by Cyagen, customized services can be provided for different point mutations to meet the experimental needs of researchers.

The MSH3 gene is a critical component of the post-replicative DNA mismatch repair (MMR) system that maintains genomic stability. It encodes the MSH3 protein, which serves as a housekeeping protein and is ubiquitously expressed at low levels across a wide range of human tissues, including the colon, rectum, small intestine, brain, and reproductive organs ^[1]. The protein primarily functions by forming a heterodimer with MSH2 to create the MutSβ complex, which is specialized in recognizing and initiating the repair of large insertion-deletion loops (IDLs) and dinucleotide or longer microsatellite repeats. Beyond its canonical MMR role, MSH3 is involved in homologous recombination and the repair of DNA double-strand breaks, contributing to cellular resistance against platinum-based chemotherapeutics ^[2]. Furthermore, MSH3 has been identified as a key genetic modifier of repeat expansion diseases, such as Huntington’s disease and myotonic dystrophy type 1, where its activity paradoxically promotes the somatic expansion of toxic CAG/CTG repeats, thereby influencing disease onset and progression ^[3]. The huMSH3 mouse is a humanized model constructed through gene-editing technology, in which the exon 7 to downstream of exon 24 of mouse Msh3 is replaced with the entire human MSH3 gene plus human MSH3 promoter and downstream region, and the human sequence is inserted in reverse to prevent disruption of the Dhfr gene function. This model can be used for research on Huntington’s disease (HD) and myotonic dystrophy type 1 (DM1), as well as for screening, development, and preclinical evaluation of MSH3-targeted therapeutics.