Ifnar1 KO Mice

Catalog Number: C001268

Strain Name: C57BL/6NCya-Ifnar1em1/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

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.

Strain Strategy


Figure 1. Gene editing strategy of Ifnar1 KO mice. The mouse Ifnar1 gene is located on chromosome 16, and Exon 2 of this gene has been knocked out using gene editing technology.


Application

Ifnar1 KO mice can be used to study antiviral immune responses, as well as interferon stimulation and JAK-STAT signaling.

 

Validation Data

1. Proportion of immune cells in the bone marrow

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


b. CD11b+ myeloid cell, macrophage, dendritic cell (DC) and granulocyte

Figure 2. Flow cytometry analysis of T lymphocytes, B lymphocytes, natural killer cells (NKC), myeloid cells (CD11b+), macrophages, dendritic cells (DC), and granulocytes in the bone marrow of Ifnar1 KO mice. The results show no significant differences in the proportions of T, B, and NK cells, as well as macrophages and dendritic cells, compared to wild-type (WT) mice. However, the proportion of CD11b+ myeloid cells and granulocytes is significantly increased.


2. Proportion of immune cells in the spleen

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


d. CD11b+ myeloid cell, macrophage, dendritic cell (DC) and granulocyte

Figure 3. Flow cytometry analysis of T lymphocytes, B lymphocytes, natural killer cells (NKC), myeloid cells (CD11b+), macrophages, dendritic cells (DC), and granulocytes in the spleen of Ifnar1 KO mice. The results show no significant differences in the proportions of T, B, and NK cells, as well as CD11b+ myeloid cells, macrophages, dendritic cells, and granulocytes, compared to wild-type (WT) mice.

3. Proportion of immune cells in the peripheral blood

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


f. CD11b+ myeloid cell, macrophage, dendritic cell (DC) and granulocyte

Figure 4. Flow cytometry analysis of T lymphocytes, B lymphocytes, natural killer cells (NKC), myeloid cells (CD11b+), macrophages, dendritic cells (DC), and granulocytes in the peripheral blood of Ifnar1 KO mice. The results show no significant differences in the proportions of T, B, and NK cells, as well as CD11b+ myeloid cells, macrophages, dendritic cells, and granulocytes, compared to wild-type (WT) mice.

 

Publications

[1] Wei Y, Gao J, Kou Y, Liu M, Meng L, Zheng X, Xu S, Liang M, Sun H, Liu Z, Wang Y. The intestinal microbial metabolite desaminotyrosine is an anti-inflammatory molecule that modulates local and systemic immune homeostasis. FASEB J. 2020 Dec;34(12):16117-16128.
[2] Zhang Y, Li Z, Ye Z, Xu Y, Wang B, Wang C, Dai Y, Lu J, Lu B, Zhang W, Li Y. The activation of antiviral RNA interference not only exists in neural progenitor cells but also in somatic cells in mammals. Emerg Microbes Infect. 2020 Dec;9(1):1580-1589.
[3] Zhang Y, Dai Y, Wang J, Xu Y, Li Z, Lu J, Xu Y, Zhong J, Ding SW, Li Y. Mouse circulating extracellular vesicles contain virus-derived siRNAs active in antiviral immunity. EMBO J. 2022 Jun 1;41(11):e109902.