Cd11b-hCD89 (FCAR) Mice

Catalog Number: C001563

Strain Name: C57BL/6NCya-Itgamtm1(IRES-hFCAR)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Heterozygote x WT

 

Strain Description

CD89, also known as Fcα receptor (FCAR), is a receptor on the surface of various immune cells and belongs to the Fc receptor family. Fc receptors bind antibodies, linking the immune system’s recognition of pathogens with cellular immune responses. CD89 is primarily expressed on monocytes/macrophages, neutrophils, eosinophils, dendritic cells, and Kupffer cells in the liver, unlike other Fc receptors expressed on lymphocytes [1]. The function of CD89 primarily involves binding with IgA antibodies (especially IgA1 and IgA2), initiating various immune responses. CD89 can trigger phagocytosis (engulfing and destroying pathogens), antibody-dependent cellular cytotoxicity (ADCC) (killing infected or cancerous cells), and release inflammatory mediators (promoting inflammatory responses and recruiting immune cells) [2]. IgA nephropathy (IgAN) is a disease closely associated with CD89 and is the most common form of glomerulonephritis, characterized by the deposition of IgA (particularly IgA1) in the glomeruli. As the myeloid cell-specific Fc receptor for IgA, CD89 specifically binds IgA1, a highly glycosylated IgA subtype predominantly found in serum and responsible for neutralizing pathogens at mucosal surfaces [3-4]. In IgA nephropathy, one pathological mechanism is the formation of immune complexes between aberrantly glycosylated IgA1 and CD89. These complexes deposit in the glomerular mesangium, activate mesangial cells and trigger inflammation, fibrosis, and kidney structural damage. Without treatment, the condition can progress to chronic kidney disease (CKD) and even end-stage renal disease (ESRD) [5-7].

Since mice lack a homologous gene to human CD89, introducing the human CD89 gene into mice aids in studying immune mechanisms and IgA nephropathy (IgAN). The Cd11b-hCD89 (FCAR) mouse is a humanized model constructed by integrating the coding sequence (CDS) of the human CD89 gene downstream of the stop codon in the mouse Cd11b (Itgam) gene. The human CD89 gene, regulated by the mouse Cd11b gene promoter, is specifically expressed in myeloid cells. Cd11b-hCD89 (FCAR) mice successfully express the human FCAR gene, with the human FCAR protein detectable in peritoneal myeloid cells. Therefore, Cd11b-hCD89 (FCAR) mice can be used to study immune responses, autoimmune mechanisms, tumors, and infectious diseases. They can also be crossed with IgA1 humanized mouse models (catalog number: C001565) to create IgA nephropathy (IgAN) mouse models that better reflect human genetic mechanisms and pathological phenotypes [8], facilitating research into IgAN mechanisms and the development of therapies.

Strain Strategy

The IRES-Human FCAR CDS cassette was inserted 60-100bp downstream of the TAA stop codon in the mouse Cd11b gene.



Application

  • Research on immune responses and autoimmune mechanisms;
  • Construction and efficacy evaluation of IgA nephropathy (IgAN) models;
  • Preclinical evaluation of CD89-targeted therapies;
  • Research on tumors and infectious diseases.

 

Validation Data

1. Gene expression


Figure 1. Detection of human FCAR gene expression in wild-type (WT) mice and heterozygous Cd11b-hCD89 (FCAR) mice (KI/+) by RT-qPCR. Human FCAR gene expression in mice was detected using human-specific primers via RT-qPCR. The result shows human FCAR gene expression in the thymus and spleen of heterozygous Cd11b-hCD89 (FCAR) mice, with higher expression levels in the spleen (6 weeks old, n=3).

2. Protein expression


Figure 2. Detection of human CD89 protein expression in the peritoneum of wild-type (WT) mice and heterozygous Cd11b-hCD89 (FCAR) mice (KI/+). Human CD89 protein (hCD89) expression in mouse serum was detected via flow cytometry. Result shows that heterozygous Cd11b-hCD89 (FCAR) mice express human CD89 protein in peritoneal myeloid cells, with the proportion of leukocytes expressing both mouse Cd11b and human CD89 (mCd11b+hCD89+) exceeding 8%. Notably, there is also a significant decrease in the number of myeloid cells (mCd11b+) in the peritoneum (6 weeks old, n=3).

 

References

[1]Monteiro RC, Van De Winkel JG. IgA Fc receptors. Annu Rev Immunol. 2003;21:177-204.
[2]Ben Mkaddem S, Rossato E, Heming N, Monteiro RC. Anti-inflammatory role of the IgA Fc receptor (CD89): from autoimmunity to therapeutic perspectives. Autoimmun Rev. 2013 Apr;12(6):666-9.
[3]Bakema JE, van Egmond M. The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity. Mucosal Immunol. 2011 Nov;4(6):612-24.
[4]Robert T, Berthelot L, Cambier A, Rondeau E, Monteiro RC. Molecular Insights into the Pathogenesis of IgA Nephropathy. Trends Mol Med. 2015 Dec;21(12):762-775.
[5]Stamellou E, Seikrit C, Tang SCW, Boor P, Tesař V, Floege J, Barratt J, Kramann R. IgA nephropathy. Nat Rev Dis Primers. 2023 Nov 30;9(1):67.
[6]Suzuki H, Novak J. IgA Nephropathy: Significance of IgA1-Containing Immune Complexes in Clinical Settings. J Clin Med. 2024 Aug 1;13(15):4495.
[7]Cheung CK, Alexander S, Reich HN, Selvaskandan H, Zhang H, Barratt J. The pathogenesis of IgA nephropathy and implications for treatment. Nat Rev Nephrol. 2024 Sep 4:10.
[8]Papista C, Lechner S, Ben Mkaddem S, LeStang MB, Abbad L, Bex-Coudrat J, Pillebout E, Chemouny JM, Jablonski M, Flamant M, Daugas E, Vrtovsnik F, Yiangou M, Berthelot L, Monteiro RC. Gluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction. Kidney Int. 2015 Aug;88(2):276-85.