Basic Information

Strain Name
CB17/lcr-PrkdcscidFcgr4tm2(FCGR3A)BcgenNcr1tm1(NCR1)Bcgen/Bcgen
Catalog number
112987
Common Name
B-hCD16A/hNKP46 mice(CB-17 SCID)
Background
CB-17 SCID
Aliases
CD16, FCG3, CD16A, FCGR3, IGFR3, IMD20, FCR-10, FCRIII, CD16-II, FCGRIII, FCRIIIA, FcGRIIIA; LY94, CD335, NKP46, NK-p46
NCBI gene ID
2214, 9437

Description

  • This gene encodes a receptor for the Fc portion of immunoglobulin G, and it is involved in the removal of antigen-antibody complexes from the circulation, as well as other responses, including antibody dependent cellular mediated cytotoxicity and antibody dependent enhancement of virus infections. The receptor encoded by this gene is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide. Natural cytotoxicity receptors 1(NCR1) mediate lysis of a variety of tumor and virus-infected cells by natural killer (NK) cells. Upon engagement, NCR trigger the cytolytic activity and cytokine release of NK cells through association with ITAM-containing signaling molecules. NCR1 has been implicated in NK cell-mediated lysis of several autologous tumor and pathogen-infected cell lines.
  • The regulatory region and exons 1~5 of mouse Fcgr4 gene that encode the full-length protein were replaced by human FCGR3A(F158V) exons 1~6 and regulatory region in B-hCD16A /hNKP46 mice(CB-17 SCID) mice. The exons 1~7 of mouse NKp46 gene that encode the extracellular domain were replaced by human NKP46 exons 1~7 in B-hCD16A/hNKP46 mice(CB-17 SCID).
  • Mouse NKP46 was only detectable in wild-type CB-17 SCID mice. Human NKP46 was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice. Mouse CD16A was detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.
  • B-hCD16A/hNKP46 mice(CB-17 SCID) provide a powerful preclinical model for in vivo evaluation of anti-CD16A and NKP46 antibodies.
  • Application: For example, this product is used for pharmacodynamics and safety evaluation of anti-CD16A and NKP46 antibodies for cancers.

Targeting strategy

Gene targeting strategy for B-hCD16A/hNKP46 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(F158V) exons 1~6 and regulatory region in B-hCD16A /hNKP46 mice(CB-17 SCID) mice. The exons 1~7 of mouse NKp46 gene that encode the extracellular domain were replaced by human NKP46 exons 1~7 in B-hCD16A/hNKP46 mice(CB-17 SCID).

Protein expression analysis in spleen-NKP46

Strain specific NKP46 expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Splenocytes were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse NKP46 antibody (eBioscience™, 17-3351-82) and anti-human NKP46 antibody (Biolegend, 331916) by flow cytometry. Mouse NKP46 was only detectable in wild-type CB-17 SCID mice. Human NKP46 was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Protein expression analysis in blood-NKP46

Strain specific NKP46 expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Blood were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse NKP46 antibody (eBioscience™, 17-3351-82) and anti-human NKP46 antibody (Biolegend, 331916) by flow cytometry. Mouse NKP46 was only detectable in wild-type CB-17 SCID mice. Human NKP46 was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Protein expression analysis in bone marrow-NKP46

Strain specific NKP46 expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Bone marrow were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse NKP46 antibody (eBioscience™, 17-3351-82) and anti-human NKP46 antibody (Biolegend, 331916) by flow cytometry. Mouse NKP46 was only detectable in wild-type CB-17 SCID mice. Human NKP46 was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Protein expression analysis in spleen

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Splenocytes were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was only detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Splenocytes were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was only detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Splenocytes were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was only detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Splenocytes were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was only detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Splenocytes were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was only detectable in wild-type CB-17 SCID mice. Human CD16A was not detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID).

Protein expression analysis in blood

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Blood were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Blood were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Blood were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was weakly detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Blood were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was not detectable in wild-type CB-17 SCID mice. Human CD16A was weekly detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Blood were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was detectable in wild-type CB-17 SCID mice. Human CD16A was not detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID).

Protein expression analysis in bone marrow

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Bone marrow were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was not detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Bone marrow were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was weakly detectable in wild-type CB-17 SCID mice. Human CD16A was weakly detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID).

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Bone marrow were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Bone marrow were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was detectable in wild-type CB-17 SCID mice. Human CD16A was exclusively detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID), but not in wild-type CB-17 SCID mice.

Strain specific CD16A expression analysis in wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) by flow cytometry. Bone marrow were collected from wild-type CB-17 SCID mice (+/+) and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (H/H) (n=3, 6-week old). Protein expression was analyzed with anti-mouse CD16.2 (FcγRIV) antibody (Biolegend, 149503) and anti-human CD16 antibody (Biolegend, 302008) by flow cytometry. Mouse CD16A was detectable in wild-type CB-17 SCID mice. Human CD16A was not detectable in homozygous B-hCD16A/hNKP46 mice(CB-17 SCID).

Frequency of leukocyte subpopulations in spleen, blood and bone marrow

Frequency of leukocyte subpopulations in spleen by flow cytometry. Splenocytes (A), blood (B) and bone marrow (C) were isolated from wild-type CB-17 SCID mice and homozygous B-hCD16A/hNKP46 mice(CB-17 SCID) (n=3, 7-week-old). Flow cytometry analysis was performed to assess the frequency of leukocyte subpopulations. Percentages of NK cells, DCs, monocytes, macrophages and neutrophils in B-hCD16A/hNKP46 mice(CB-17 SCID) were similar to those in CB-17 SCID mice, demonstrating that humanization of CD16A and NKP46 does not change the frequency or distribution of these cell types in spleen, blood and bone marrow. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.

Frequency of leukocyte subpopulations in blood

Frequency of leukocyte subpopulations in blood by flow cytometry. Blood cells were isolated from female wild-type BALB/c mice (n=3, 7-week-old) and homozygous B-Rag2 KO mice(C) (n=3, 7-week-old). A. Flow cytometry analysis of the blood cells was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. The frequency of total T cells, CD4+ T cells, CD8+ T cells, Tregs and B cells were decreased in B-Rag2 KO mice(C). The frequency of NK cells, DCs, neutrophils and macrophages were increased in B-Rag2 KO mice(C) compared to BALB/c mice, demonstrating that Rag2 was successfully knocked out in blood. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***p < 0.001.

Frequency of leukocyte subpopulations in bone marrow

Frequency of leukocyte subpopulations in bone marrow by flow cytometry. Bone marrow cells were isolated from female wild-type BALB/c mice (n=3, 7-week-old) and homozygous B-Rag2 KO mice(C) (n=3, 7-week-old). A. Flow cytometry analysis of the bone marrow cells was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. The frequency of total T cells, CD4+ T cells, CD8+ T cells, Tregs and B cells were decreased in B-Rag2 KO mice(C). The frequency of NK cells, DCs, neutrophils and macrophages were increased in B-Rag2 KO mice(C) compared to BALB/c mice, demonstrating that Rag2 was successfully knocked out in bone marrow. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***p < 0.001.

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