Basic Information

Strain name
CB-17 SCID-Fcgr4tm2(FCGR3A)/Bcgen
Common name
B-hCD16A mice(CB-17 SCID)
Background
CB-17 SCID
Catalog Number
111174
Related Gene
FCGR3A (Fc fragment of IgG receptor IIIa), CD16A

Description

CD16 is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, and macrophages, and has been identified as Fc receptors FcγRIIIa (CD16a, Low affinity immunoglobulin gamma Fc region receptor III-A. FCGR3A, gene ID 2214) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16. While FcγRIIIa is expressed on mast cells, macrophages, and natural killer cells as a transmembrane receptor, FcγRIIIb is only expressed on neutrophils. In addition, FcγRIIIb is the only Fc receptor anchored to the cell membrane by a glycosyl-phosphatidylinositol (GPI) linker, and also plays a significant role in triggering calcium mobilization and neutrophil degranulation. FcγRIIIa and FcγRIIIb together are able to activate degranulation, phagocytosis, and oxidative burst, which allows neutrophils to clear opsonized pathogens. With its expression on neutrophils, CD16 represents a possible target in cancer immunotherapy. Margetuximab, an Fc-optimized monoclonal antibody that recognizes the human epidermal growth factor receptor 2 (HER2) expressed on tumor cells in breast, bladder, and other solid tumor cancers, targets CD16A in preference to CD16B. In addition, CD16 could play a role in antibody-targeting cancer therapies. FcγRIV, a murine homologue of CD16A has been shown to be involved in antibody-mediated depletion of tumor-infiltrating regulatory T cells in monoclonal antibody mediated immunotherapy. Bispecific antibody fragments, such as anti-CD19/CD16, allow the targeting of immunotherapeutic drugs to the cancer cell. Anti-CD19/CD16 diabodies have been shown to enhance the natural killer cell response to B-cell lymphomas. Furthermore, targeting extrinsic factors such as FasL or TRAIL to the tumor cell surface triggers death receptors, inducing apoptosis by both autocrine and paracrine processes.

B-hCD16A mice are provided on the CB17-SCID background, which is deficient in T and B Cells, but has intact NK cell, macrophage and granulocyte function. CB17-SCID mice survive under SPF conditions for up to a year and are fertile.

Targeting Strategy

Gene targeting strategy for B-hCD16A mice(CB-17 SCID).

The regulatory region and exons 1~5 of mouse Fcgr4 gene that encode the full-length protein were replaced by human FCGR3A exons 1~4 and regulatory region in B-hCD16A mice(CB-17 SCID).

Surface Expression in NK Cells

Species-specific FCGR3A expression analysis in wild-type CB-17 SCID mice and homozygous B-hFCGR3A(CB-17 SCID) by flow cytometry.  Splenocytes were collected from wild-type CB-17 SCID mice(+/+)  and homozygous B-hFCGR3A mice(CB-17 SCID) (H/H). Mouse FCGRIV was not detectable in NK cells of wild-type CB-17 SCID mice. Human FCGR3A was detectable in NK cells of B-hFCGR3A mice(CB-17 SCID).

Surface Expression in Granulocytes

Species-specific FCGR3A expression analysis in wild-type CB-17 SCID mice and homozygous B-hFCGR3A(CB-17 SCID)  by flow cytometry.  Splenocytes were collected from wild-type CB-17 SCID mice(+/+)  and homozygous B-hFCGR3A mice (CB-17 SCID) (H/H). Mouse FCGR3A was exclusively detectable in granulocytes of wild-type CB-17 SCID. Human FCGR3A was not detectable in granulocytes of wild-type CB-17 SCID mice and homozygous B-hFCGR3A mice (CB-17 SCID).

Surface Expression in Macrophages

Strain specific FCGR3A expression analysis in wild-type CB-17 SCID mice and homozygous B-hFCGR3A(CB-17 SCID)  by flow cytometry. Peritoneal exudative macrophages(PEMs) were collected from wild-type CB-17 SCID mice(+/+)  and homozygous B-hFCGR3A mice (CB-17 SCID) (H/H). Mouse FCGRIV was exclusively detectable in PEMs of wild-type C57BL/6 mice. Human FCGR3A was exclusively detectable in PEMs of homozygous B-hFCGR3A mice (CB-17 SCID).