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(IFNα/β/γR-DKO) 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(IFNα/β/γR-DKO) 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(IFNα/β/γR-DKO) mice exhibit more pronounced neurological symptoms after infection ^[6,9].

The protein encoded by the Angiotensin Converting Enzyme 2 (ACE2) gene belongs to the angiotensin converting enzyme family of dipeptidyl carboxydipeptidases and is homologous to Angiotensin I. ACE2 is expressed in a variety of human organs and has a strong affinity for Angiotensin I (AngⅠ) and Angiotensin II (AngⅡ) receptors. It catalyzes the cleavage of Ang I to angiotensin 1-9 (Ang1-9) and Ang II to angiotensin 1-7 (Ang1-7), which has a vasodilating and antihypertensive effect ^[1], and plays a role in the regulation of blood pressure, fluid balance, inflammation, cell proliferation, hypertrophy, and fibrosis, as well as in the regulation of cardiovascular and renal function and fertility ^[2]. ACE2 is also a common functional receptor for the spike protein of human coronavirus HCoV-NL63 and the severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV-2 ^[3]. This strain is a mouse Ace2 gene knockout model that uses gene editing technology to knock out the homologous gene of human ACE2 in mice. The knockout of the Ace2 gene will result in the absence of ACE2 protein expression, and this model can be used for the study of COVID-19. The homozygous Ace2-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 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.

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 IFNGR1 gene encodes the ligand-binding chain (α) of the type II (γ) interferon receptor. IFNGR1 forms a receptor complex with IFNGR2, which can bind gamma interferon and participate in immune and inflammatory responses. The G129(Ifngr1-KO) mice on a 129 background are a type II (γ) interferon receptor (Ifngr1) gene knockout model. The absence of the IFNGR1 protein in these mice results in defective gamma interferon receptor function, which reduces natural resistance and may increase susceptibility to certain viral infections. Homozygous G129(Ifngr1-KO) mice are viable and fertile.

Angiotensin-converting enzyme 2 (ACE2) is the predominant cell surface receptor for SARS-CoV-2 virus infection in humans, but due to interspecies differences, the SARS-CoV-2 virus is unable to bind to ACE2 receptors in most wild-type rodents, including mice. Replacement of mouse Ace2 with human ACE2 by gene editing techniques resulted in humanized ACE2 mice (hACE2) that stably express human ACE2 receptors for COVID-19 studies. This strain is a mouse Ace2 gene humanization model that uses gene editing technology to replace the endogenous mouse Ace2 gene sequence with human ACE2 CDS, preserving the mouse signal peptide sequence and achieving hACE2 expression directed by the endogenous mouse Ace2 regulatory element. This gene is located on the mouse chromosome X. Homozygous females and heterozygous males are viable and fertile.

Angiotensin-converting enzyme 2 (ACE2) is the predominant cell surface receptor for SARS-CoV-2 virus infection in humans, but due to interspecies differences, the SARS-CoV-2 virus is unable to bind to ACE2 receptors in most wild-type rodents, including mice. Replacement of mouse Ace2 with human ACE2 by gene editing techniques resulted in humanized ACE2 mice (hACE2) that stably express human ACE2 receptors for COVID-19 studies. This strain is a mouse Ace2 gene humanization model that uses gene editing technology to replace the endogenous mouse Ace2 gene sequence with human ACE2 CDS, preserving the mouse signal peptide sequence and achieving hACE2 expression directed by the endogenous mouse Ace2 regulatory element. This gene is located on the mouse chromosome X, and homozygous females and heterozygous males are viable and fertile.

Angiotensin-converting enzyme 2 (ACE2) is a member of the angiotensin-converting enzyme (ACE) family of dipeptidyl carboxypeptidases. ACE2 is expressed in a variety of human tissues and has a high affinity for angiotensin I (Ang I) and angiotensin II (Ang II) receptors. ACE2 catalyzes the cleavage of Ang I to angiotensin 1-9 (Ang 1-9) and Ang II to angiotensin 1-7 (Ang 1-7), which have vasodilatory and hypotensive effects ^[1]. ACE2 plays a role in regulating blood pressure, fluid balance, inflammation, cell proliferation, hypertrophy, and fibrosis, as well as in the regulation of cardiovascular and renal function and fertility ^[2]. ACE2 is also the common functional receptor for the spike protein of human coronaviruses HCoV-NL63, SARS-CoV, and SARS-CoV-2 ^[3]. However, due to species differences, the SARS-CoV-2 virus cannot bind to the ACE2 receptor of wild-type rodents ^[4-5]. Replacement of mouse Ace2 with human ACE2 by gene editing techniques resulted in humanized ACE2 mice (hACE2) that stably express human ACE2 receptors for COVID-19 studies. This strain contains a loxP-hACE2 CDS-loxP gene expression cassette inserted at the endogenous mouse Ace2 gene locus, which enables the regulation of human ACE2 gene (hACE2) expression by the mouse endogenous Ace2 regulatory element. When bred with relevant tissue-specific Cre mouse mating, knockout of the hACE2 gene can be achieved in specific tissues of the offspring mice. Homozygous hACE2-flox mice are viable and fertile.