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.

The ATP7B gene encodes a copper-transporting ATPase β-peptide that is a member of the P-type cation-transporting ATPase family, which uses the energy stored in adenosine triphosphate (ATP) molecules to transport metals into and out of cells. The ATP7B protein consists of multiple transmembrane structural domains, an ATPase consensus sequence, a hinge structural domain, and a phosphorylation site, as well as at least two putative copper-binding sites ^[1]. This protein is found mainly in the liver and to a lesser extent in the kidney and brain, and functions as a copper-transporting ATPase that plays a role in transporting copper from the liver to other parts of the body. Copper is an important component of certain enzymes that maintain normal cellular function, and the ATP7B protein is important for the removal of excess copper from the body. Mutations in this gene are associated with Wilson disease (WD), which is characterized by the accumulation of copper to toxic levels that damage tissues and organs such as the liver and brain as the removal of excess copper from the body is compromised with the absence of the functional ATP7B protein ^[2-4]. This strain is an Atp7b deletion mouse model, which uses gene editing technology to knock out Atp7b, the homolog of the human ATP7B gene in mice that lack the expression of ATP7B protein and can be used in the study of disorders related to copper metabolisms such as Wilson's disease, acute liver failure, and steatohepatitis. The heterozygous Atp7b KO mice are viable and fertile, and homozygous mice have a reduced life expectancy.

Interferons (IFNs) are potent cytokines that serve as a critical component of the body's first line of defense against viral infections, playing a key role in inflammation and immune control by directly inducing pathogen-inhibiting molecules that suppress viral replication ^[1]. Arthropod-borne viruses (arboviruses) like Dengue virus (DENV), Zika virus (ZIKV), and Yellow Fever virus (YFV) encode proteins that antagonize the IFN response, helping these viruses evade host immunity and maintain sufficient viral loads in the blood (viremia) to sustain the vector-host transmission. Arboviruses pose a significant public health threat, affecting around 3.9 billion people in tropical and subtropical regions. However, most preclinical studies suggest that arboviruses cannot inhibit IFN responses in mice, rendering immunocompetent mice resistant to infection, with low viral loads and limited circulation, thus limiting their use in infection research ^[2-3]. As a result, immunodeficient mouse models with defects in multiple IFN signaling pathways have become essential tools for studying arbovirus pathogenesis and vaccine development ^[2-4]. Studies have demonstrated that wild-type mice of strains like C57BL/6, CD-1, or 129 rarely exhibit clinical symptoms after infection with arboviruses such as ZIKV. However, the virus has been detected in the blood, ovaries, and spleen of ZIKV-infected 129 mice, suggesting that this strain may be more susceptible to arboviruses ^[5-6]. Because the virus can persist in the bloodstream without causing disease or death, the 129 strain can be used to evaluate the teratogenic effects of such viruses. Furthermore, the 129 strain is commonly used in interferon signaling-deficient models related to other viral infections ^[7-8]. The IFNAR1 gene encodes a key component of the type I IFN receptor, while the IFNGR1 gene encodes the ligand-binding chain (α) of the type II (γ) IFN receptor. AG129 mice, which are knockout models for both the type I (α/β) IFN receptor (Ifnar1) and the type II (γ) IFN receptor (Ifngr1), lack functional IFNAR1 and IFNGR1 proteins, resulting in deficiencies in α/β/γ interferon receptor signaling and heightened susceptibility to viral infections. Homozygous AG129 mice are viable and fertile, and exhibit increased sensitivity to arboviral infections, generating viremia similar to that seen in humans. Compared to IFNα/β/γR KO mice on the C57BL/6 background, the 129-background AG129 mice exhibit more pronounced neurological symptoms after infection ^[6,9].

Adiponectin, a protein hormone encoded by the ADIPOQ gene, is exclusively produced by adipocytes. It is secreted into the bloodstream and transported to muscle and liver cells, playing a crucial role in maintaining glucose and lipid metabolic homeostasis. Adiponectin participates in the regulation of glucose metabolism, lipolysis, and energy balance by promoting fatty acid oxidation, enhancing insulin sensitivity, and modulating metabolic signaling pathways such as AMPK. Additionally, it exhibits biological functions including anti-inflammatory and anti-atherosclerotic effects, as well as the amelioration of insulin resistance ^[1-3]. Aberrant ADIPOQ expression is closely associated with various metabolic disorders, including obesity, type 2 diabetes, metabolic syndrome, fatty liver disease, and cardiovascular diseases ^[1-4]. Although the ADIPOQ gene is expressed exclusively in adipose tissue, adiponectin is widely distributed across multiple organs, including muscle, liver, intestine, male reproductive glands, and the brain ^[3-4]. The Adipoq-P2A-iCreERT2 mouse was generated by inserting a P2A-iCreERT2 expression cassette at the stop codon of the endogenous mouse Adipoq gene. The regulatory elements of the mouse Adipoq gene drive the expression of the iCreERT2 recombinase. In the absence of tamoxifen, the iCreERT2 recombinase is predominantly retained in the cytoplasm; upon tamoxifen induction, the recombinase translocates into the nucleus to exert its recombinase activity. When Adipoq-P2A-iCreERT2 mice are crossed with mice carrying loxP sites, the resulting offspring are expected to undergo Cre-mediated recombination of sequences flanked by loxP sites within adipose tissue following tamoxifen induction.

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.

Stargardt disease (STGD), a hereditary macular dystrophy, is characterized by the presence of yellowish flecks within the retinal pigment epithelium (RPE), ultimately culminating in macular atrophy. Typically manifesting in childhood and adolescence, STGD leads to progressive central vision loss and mild dyschromatopsia. Fundoscopic examination may reveal pale yellow lesions exhibiting a characteristic gold foil-like sheen, accompanied by yellow-white spots surrounding the posterior pole. In advanced stages, atrophy of the RPE, photoreceptors, and choriocapillaris is observed. This bilateral and typically synchronous condition affects both eyes with comparable incidence across sexes, estimated between 1/8,000 and 1/13,000. STGD is predominantly an autosomal recessive disorder, with mutations in the ABCA4 gene accounting for approximately 95% of cases. ABCA4 encodes a retina-specific ABC transporter protein crucial for the clearance of retinal derivatives and toxic metabolites generated during rhodopsin photobleaching. Consequently, ABCA4 mutations result in the accumulation of these cytotoxic substances, triggering apoptosis of both RPE and photoreceptor cells and ultimately driving retinal degeneration. Notably, ABCA4 mutations have been implicated in a spectrum of retinal diseases, including STGD, cone-rod dystrophy (CRD), age-related macular degeneration (AMD), and retinitis pigmentosa (RP), with the specific clinical phenotype correlating with the nature and severity of the ABCA4 mutation. This strain is an Abca4 gene knockout (KO) mouse model. Gene-editing technology was used to delete the protein-coding sequence of the Abca4 gene (the homolog of the human ABCA4 gene) in mice. Previous studies have demonstrated that Abca4 KO mice exhibit delayed dark adaptation following photobleaching and a slow progression of photoreceptor degeneration^[1]. Homozygous Abca4-KO mice are viable and fertile.

The ALMS1 gene encodes the large, multi-domain ALMS1 protein, which localizes primarily to the centrosomes and basal bodies of primary cilia within cells. There, it plays a critical role in microtubule organization, ciliogenesis, endosome recycling (notably of the GLUT4 transporter), and cell cycle regulation ^[1]. Because primary cilia are sensory organelles found on nearly all cell types, the gene is expressed across a wide range of tissues, including the retina, cochlea, pancreatic islets, adipose tissue, renal tubules, and cardiomyocytes. Mutations in ALMS1 lead to Alström syndrome in humans, a rare autosomal recessive ciliopathy marked by progressive multisystem failure, including cone-rod dystrophy (blindness), sensorineural hearing loss, childhood obesity, extreme insulin resistance, type 2 diabetes, and dilated cardiomyopathy ^[2]. Research on mice with Alms1 deficiency has successfully recapitulated the clinical features mentioned above, confirming that the loss of this gene leads to stunted renal cilia, impaired intracellular trafficking in photoreceptors, and metabolic dysfunction that mirrors human disease progression ^[3]. Furthermore, a high-fat diet (HFD) can accelerate the metabolic pathological process in Alms1 KO mice, making them more susceptible to metabolic diseases such as hyperglycemia, hyperinsulinemia, and insulin resistance, while also inducing hepatic inflammation and fibrosis ^[4]. Alms1-del(c.3802-3812) mice are a research model constructed using gene-editing technology to introduce a c.3802_3812 del CAAAAACAGTT mutation into exon 8 of the mouse Alms1 gene. Both homozygous female and male Alms1-del(c.3802-3812) mice were infertile. This model can be utilized for research into the pathological mechanisms and the development of therapeutic interventions for Alström syndrome, as well as metabolic diseases such as obesity, diabetes, and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

The Cre-P2A cassette was inserted upstream of the ATG start codon.

The TAA stop codon was replaced with the P2A-CreERT2 cassette. CreERT2 recombinase is expressed under the regulatory control of Adgre1 gene elements. This model is a Tamoxifen-inducible Cre mouse, and when crossed with mice containing loxP sites, the offspring mice are expected to undergo sequence recombination between loxP sites mediated by Cre recombinase in macrophages following Tamoxifen induction.