B6-IgG1 KO Mice

Catalog Number: C001390

Strain Name: C57BL/6JCya-Ighg1em1/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote x Homozygote

 

Strain Description

Immunoglobulin G (IgG) is the most abundant type of immunoglobulin in human serum, accounting for about 75% of the total serum immunoglobulins. It also has the longest half-life among serum immunoglobulins. IgG is synthesized in the spleen and lymph nodes and is primarily distributed in serum and tissue fluids. It is a major component of antibodies against bacteria, toxins, and viruses, and plays a crucial role in the body's immune response against infections. IgG is the only immunoglobulin that can cross the placental barrier, playing an important role in neonatal infection protection [1]. There are four IgG subtypes in the human body, with the IgG1 subtype accounting for about 66% of the total serum IgG. IgG1 is very important for mediating antibody responses against viral pathogens. It can effectively bind to C1q, triggering complement-dependent cytotoxicity (CDC), and bind to various Fc receptors, inducing antibody-dependent cell-mediated cytotoxicity (ADCC). These are two of the most important functions in immune responses. Therefore, IgG1 has always been the preferred model for antibody therapy and is the most promising subtype in tumor immunotherapy [2-3].

Selective IgG Subclass Deficiency is one of the most common immunodeficiency diseases in children. Patients with this disease have reduced total serum IgG levels, or normal total IgG levels but one or more IgG subclasses below normal levels. In most cases, patients with IgG1 deficiency also have deficiencies in other IgG subclasses, often with low serum IgG levels. Those with deficiencies in other IgG categories are prone to developing common variable immunodeficiency (CVID). Patients usually have a lifelong history of susceptibility to pyogenic infections, which can develop into chronic, progressively worsening lung infections, and commonly have deficient antibody responses to diphtheria and tetanus toxins [4-5].

The mouse Ighg1 gene is homologous to the human IGHG1, IGHG2, and IGHG3 genes. B6-IgG1 KO mice are constructed by knocking out the Ighg1 gene in mice, creating a model of IgG1 deficiency. This model provides an effective tool for research on diseases related to IgG1 deficiency.

Strain Strategy

The Ighg1 gene is located on chromosome 12 in mice. Using gene-editing technology, exons 1 to 6 of this gene have been knocked out.


Application

  • Research on IgG1 Deficiency Diseases;
  • Research on Hypogammaglobulinemia Related to IgG Deficiency;
  • Study of the Mechanisms and Functions of Immunoglobulin G (IgG).

 

Validation Data

1. Serum IgG Level

Figure 1. Detection of IgG1 Levels in the Serum of 8-Week-Old B6-IgG1 KO Mice and Wild-Type Mice. Peripheral blood was collected from B6-IgG1 KO mice (IgG1-KO) and wild-type mice (WT) to isolate serum. The IgG1 levels in the serum were detected using ELISA. The results show a significant difference in the IgG1 levels between B6-IgG1 KO mice and wild-type mice, with nearly no IgG1 expression in the serum of the B6-IgG1 KO mice.

2. Summary

An IgG1 deficiency model mouse was constructed by using gene-editing technology to knock out the Ighg1 gene in mice. The model mice were evaluated using serum ELISA detection. The results showed that, compared to wild-type control mice, the serum IgG1 expression levels in B6-IgG1-KO mice were significantly reduced, with almost no expression, confirming the successful establishment of the model. This model can be used for subsequent research on diseases related to IgG1 deficiency, providing a strong and effective tool for human disease research.

 

References
[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.
[4]O'Keeffe S, Finnegan P. IgG subclass deficiency. Chest. 1993 Dec;104(6):1940.
[5]Barton JC, Barton JC, Bertoli LF, Acton RT. Factors associated with IgG levels in adults with IgG subclass deficiency. BMC Immunol. 2021 Aug 9;22(1):53.