B6-hFCGR1 Mouse
Product Name
B6-hFCGR1 Mouse
Product ID
C001500
Strain Name
C57BL/6NCya-Fcgr1tm1(hFCGR1A)/Cya
Backgroud
C57BL/6NCya
When using this mouse strain in a publication, please cite “B6-hFCGR1 Mouse (Catalog C001500) were purchased from Cyagen.”
Product Type
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Datasheet
Strain Description
FCGR1 gene encodes FcγRI, a specific receptor for IgG antibodies, also known as CD64. This receptor plays a key role in human immune responses. FcγRI has a high affinity for the Fc portion of IgG antibodies and is the only member of the human FcγRs with a high affinity for monomeric IgG. It plays important roles in both innate and adaptive immune responses [1]. FcγRI is expressed on a variety of immune cells, including monocytes, macrophages, dendritic cells, and neutrophils. It plays a critical role in host defense against infection and humoral immunity by influencing processes such as phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and antigen presentation [2-3]. The binding of FcγRI to IgG-coated target cells promotes their phagocytosis by immune cells. This is an important mechanism for clearing infected cells, apoptotic cells, and other foreign particles. In addition, this binding can also promote the release of cytotoxic granules by immune cells, such as natural killer cells and cytotoxic T cells, leading to the killing and lysis of target cells. In antigen presentation, FcγRI binding to IgG-coated antigens promotes dendritic cells to take them up and present them to T cells, which is essential for the initiation of adaptive immune responses. In addition, FcγRI is involved in a variety of important physiological processes, such as wound healing and inflammation. FcγRI plays a critical role in antibody-based immunotherapy, which has important implications for the development of therapeutic drugs and methods for a variety of autoimmune diseases, infectious diseases, and tumors [4-5].
This model represents a humanized FCGR1 mouse, generated by substituting the mouse Fcgr1 gene sequence (inclusive of the UTR) with the corresponding human FCGR1 gene sequence. This modification enables the expression of human FcγRI in mice. Homozygous B6-hFCGR1 mice exclusively express human FcγRI receptors, with the proportion of cells expressing human FcγRI mirroring that of cells expressing mouse FcγRI in wild-type mice. Consequently, this model serves as a valuable tool for various research areas, including the evaluation of human IgG antibody affinity, exploration of the ADCC mechanism, investigation into immune cell phagocytosis and antigen presentation. Furthermore, it provides a platform for the preclinical assessment of therapeutic human IgG antibodies.
Reference
van der Poel CE, Spaapen RM, van de Winkel JG, Leusen JH. Functional characteristics of the high affinity IgG receptor, FcγRI. J Immunol. 2011 Mar 1;186(5):2699-704.
Lu J, Chu J, Zou Z, Hamacher NB, Rixon MW, Sun PD. Structure of FcγRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding. Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):833-8.
Junker F, Gordon J, Qureshi O. Fc Gamma Receptors and Their Role in Antigen Uptake, Presentation, and T Cell Activation. Front Immunol. 2020 Jul 3;11:1393.
Hogarth PM, Pietersz GA. Fc receptor-targeted therapies for the treatment of inflammation, cancer and beyond. Nat Rev Drug Discov. 2012 Mar 30;11(4):311-31.
Holtrop T, Budding K, Brandsma AM, Leusen JHW. Targeting the high affinity receptor, FcγRI, in autoimmune disease, neuropathy, and cancer. Immunother Adv. 2022 May 28;2(1):ltac011.
Strain Strategy
The mouse Fcgr1 gene sequence was completely replaced with the corresponding sequence in the human FCGR1A gene by gene editing technology.
Figure 1. Diagram of the gene editing strategy for the generation of B6-hFCGR1 mice.
Application Area
Studies of antibody-dependent cell-mediated cytotoxic effects (ADCC);
Phagocytosis and antigen presentation studies of the immune system;
Drug affinity, pharmacology, and efficacy assessment based on FcγRI receptor IgG antibodies.
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