B6-hIGHG1 Mice

Catalog Number: C001401

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

Strain Description

IgG is the type of immunoglobulin with the highest concentration in human serum, accounting for about 75% of the total amount of immunoglobulin. It has the longest half-life among all immunoglobulins. IgG synthesized in the spleen and lymph nodes is mainly distributed in serum and tissue fluids and is the main component of antibacterial, antitoxin, and antiviral antibodies. It plays an important role in the immune response to infection and is the only immunoglobulin that can pass through the placental barrier, providing newborns with resistance to infection ^[1]. There are four IgG subtypes in the human, with IgG1 accounting for approximately 66% of IgG in serum. IgG1 is crucial for mediating antibody responses against viral pathogens. It can effectively bind to C1q, causing complement-dependent cytotoxicity (CDC), and can bind to each different Fc receptor, causing antibody-dependent cell-mediated cytotoxicity (ADCC). These are the two most important functions in the immune response. Therefore, IgG1 has always been the preferred mode of antibody therapy and the most promising subtype in tumor immunotherapy ^[2-3].

Immunoglobulin heavy constant gamma 1 (G1m marker) (IGHG1) gene encodes the constant region of IgG1. It is associated with diseases such as chronic lymphocytic leukemia and amyloidosis and plays an important role in various processes, including activating immune responses, resisting other organisms, and phagocytosis. It is also involved in the positive regulation of immune and allergic reactions and phagocytosis. IGHG1 also promotes the proliferation, migration, and chemotherapy resistance of certain malignant tumors. Additionally, pathways related to IGHG1 include the SARS-CoV-2 signaling pathway and the immunoreceptor tyrosine-based activation motif (ITAM)-mediated complement pathway.

This strain is a mouse IgG1-C-terminal humanized model. The 2-4 exon encoding hinge region, CH2 domain, and CH3 domain in the mouse Ighg1 gene were replaced with corresponding human gene sequences. Human IGHG1 expression can be detected in the spleen and serum, making this model useful for research on the mechanism of immunoglobulin, IgG antibody development and screening, as well as tumor proliferation, migration, and chemotherapy resistance.

Strain Strategy

Figure 1. The gene editing strategy for generating B6-hIGHG1 mice. The mouse Ighg1 locus hinge (exon2), CH2 (exon3), and CH3 (exon4) regions were replaced with human hinge (exon2), CH2 (exon3), and CH3 (exon4) sequences.

Validation Data

1. Detection of human IgG1 in serum

Figure 2. Detection of IgG1 content in the serum of B6-hIGHG1 mice and wild-type mice. Peripheral blood was collected from B6-hIGHG1 mice and wild-type mice (C57BL/6N), and serum was obtained. The human IgG1 was detected by ELISA. The results showed that human IgG1 expression was present in the B6-hIGHG1 mice, while there was no human IgG1 expression in wild-type mice.

 

2. Detection of human IGHG1 mRNA expression in the spleen

Figure 3. Detection of human IGHG1 mRNA in the spleen of B6-hIGHG1 mice and wild-type mice. The expression of human IGHG1 mRNA in the spleen was analyzed by PCR. The results showed that compared with the control group (C57BL/6N), B6-hIGHG1 mice had significant human IGHG1 mRNA expression in the spleen.

Reference

[1] Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014 Oct 20;5:520.

[2] de Taeye SW, Bentlage AEH, Mebius MM, Meesters JI, Lissenberg-Thunnissen S, Falck D, Sénard T, Salehi N, Wuhrer M, Schuurman J, Labrijn AF, Rispens T, Vidarsson G. FcγR Binding and ADCC Activity of Human IgG Allotypes. Front Immunol. 2020 May 6;11:740.

[3] Pereira NA, Chan KF, Lin PC, Song Z. The "less-is-more" in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity. MAbs. 2018 Jul;10(5):693-711.