G129 (Ifngr1 KO) Mice

Catalog Number: I001200

Strain Name: 129S2/SvPasCya-Ifngr1em1/Cya

Genetic Background: 129S2/SvPasCya

Reproduction: Homozygote x Homozygote

 

Strain Description

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.

Strain Strategy

The Ifngr1 gene on mouse chromosome 10 was knocked out by deleting exons 2-6 using gene-editing technology.


Application

  • Investigating the pathogenesis and developing vaccines for arboviruses such as DENV, ZIKV, YFV, and CHIKV.
  • Studying antiviral immune responses, interferon stimulation, and JAK-STAT signaling.

 

Validation Data

1. Expression of the Ifngr1 gene


Figure 1. Mouse gene expression in the brain, duodenum, and thymus of wild-type mice (WT) and G129 (Ifngr1 KO) mice. RT-qPCR results show that the Ifngr1 gene expression is completely knocked out in the brain, duodenum, and thymus of G129 (Ifngr1 KO) mice.

ND: Not detected.

2. Proportion of immune cells in peripheral blood

a. Lymphocyte (T, B) and natural killer cell (NKC) testing


b. CD11b+ myeloid, macrophage, dendritic, and granulocyte testing


Figure 2. Flow cytometry analysis of T lymphocytes, B lymphocytes, natural killer cells (NKC), total myeloid cells (CD11b+), macrophages, dendritic cells (DC), and granulocytes in the peripheral blood of G129 (Ifngr1 KO) mice. The results show that, compared to wild-type mice (WT), G129 (Ifngr1 KO) mice exhibit an increased proportion of T cells and a decreased proportion of B cells and NK cells in peripheral blood. Additionally, G129 (Ifngr1 KO) mice show a reduced proportion of total myeloid cells (CD11b+) in peripheral blood, with no significant differences in the proportions of granulocytes, macrophages, and dendritic cells.



References

[1]Müller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM, Aguet M. Functional role of type I and type II interferons in antiviral defense. Science. 1994 Jun 24;264(5167):1918-21.
[2]van den Broek MF, Müller U, Huang S, Zinkernagel RM, Aguet M. Immune defence in mice lacking type I and/or type II interferon receptors. Immunol Rev. 1995 Dec;148:5-18.
[3]Marín-Lopez A, Calvo-Pinilla E, Moreno S, Utrilla-Trigo S, Nogales A, Brun A, Fikrig E, Ortego J. Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor. Viruses. 2019 Jan 8;11(1):35.
[4]Grant A, Ponia SS, Tripathi S, Balasubramaniam V, Miorin L, Sourisseau M, Schwarz MC, Sánchez-Seco MP, Evans MJ, Best SM, García-Sastre A. Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling. Cell Host Microbe. 2016 Jun 8;19(6):882-90.
[5]Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E, Miner JJ, Diamond MS. A Mouse Model of Zika Virus Pathogenesis. Cell Host Microbe. 2016 May 11;19(5):720-30.
[6]Rossi SL, Tesh RB, Azar SR, Muruato AE, Hanley KA, Auguste AJ, Langsjoen RM, Paessler S, Vasilakis N, Weaver SC. Characterization of a Novel Murine Model to Study Zika Virus. Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-1369.
[7]Meyts I, Casanova JL. Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway. Eur J Immunol. 2021 May;51(5):1039-1061.
[8]Zivcec M, Spiropoulou CF, Spengler JR. The use of mice lacking type I or both type I and type II interferon responses in research on hemorrhagic fever viruses. Part 2: Vaccine efficacy studies. Antiviral Res. 2020 Feb;174:104702.