The Ifnar1 gene encodes the interferon-alpha/beta receptor 1 subunit, a critical mediator of the body's antiviral and immune responses. This gene is predominantly expressed in immune cells, including lymphocytes and dendritic cells, and is also present in various tissues such as the liver, brain, and skin. The protein product of Ifnar1 forms a receptor complex with Ifnar2, which is essential for the binding of interferons alpha and beta. This ligand-receptor interaction initiates a cascade of signaling pathways, culminating in the activation of genes responsible for antiviral protein production, cell growth inhibition, and immune cell recruitment. The Ifnar1 gene plays a pivotal role in host defense, regulating a broad spectrum of processes including cellular growth, survival, differentiation, pathogen resistance, and antiviral immunity. Mutations or dysregulation of Ifnar1 can result in severe pathologies, such as systemic lupus erythematosus, characterized by excessive immune activation and tissue damage, or certain cancers, where compromised interferon signaling undermines anti-tumor immunity. This strain represents a model of Ifnar1 knockout (KO), constructed by the deletion of exon 2 (E2) of the mouse Ifnar1 gene. This modification leads to a deficiency in the function of type I IFN receptors, resulting in a diminished immune response, heightened susceptibility to viral infections, and a decreased immune response to immunostimulatory DNA. Homozygous Ifnar1 KO mice are viable and fertile.

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].

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 protein that is an essential component of the type I interferon (IFN) receptor, playing a critical role in the antiviral and immune responses. IFNAR1 is primarily expressed in immune cells, such as lymphocytes and dendritic cells, and various tissues, including the liver, brain, and skin. Defects in IFNAR1, whether due to mutations or regulatory abnormalities, can lead to severe diseases such as systemic lupus erythematosus, where excessive immune activation results in tissue damage, and certain cancers. Other diseases associated with IFNAR1 include hepatitis C, yellow fever, measles, papilloma, and viral infections. The A129 (Ifnar1 KO) mice on a 129 background are a type I (α/β) interferon receptor (Ifnar1) gene knockout model. The absence of the IFNAR1 protein in these mice leads to a lack of type I IFN receptor function, thereby reducing immune response and increasing susceptibility to viral infections. Homozygous A129 (Ifnar1 KO) mice are viable and fertile, but they show increased susceptibility to arbovirus infections.

Tmem132a is located on chromosome 19 of mice. Nuclease Technology was used to design sgRNA; Tmem132a knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Spag17 is located on chromosome 3 of mice. SgRNA and ssDNA will be designed using Nuclease Technology; Spag17 conditional knockout mice will be obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm will be collected for cryopreservation.

Ifnar1 is located on chromosome 16 of mice. Nuclease Technology was used to design sgRNA; Ifnar1 knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Ifnar1 is located on chromosome 16 of mice. SgRNA and ssDNA were designed using Nuclease Technology; Ifnar1 conditional knockout mice were obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.