Basic Information

Strain name
C57BL/6-Vsig4tm1(VSIG4)/Bcgen
Common name
B-hVSIG4 mice
Background
C57BL/6
Catalog number
111035
Aliases
CRIg, Z39IG
NCBI Gene ID

Gene Targeting Strategy

Biocytogen replaced the murine Vsig4 gene by inserting human VSIG4 and murine 3’UTR coding sequences into exon 2.

mRNA Expression Analysis

Species-specific VSIG4 gene expression analysis in wild-type C57BL/6 mice and humanized B-hVSIG4 mice. Murine Vsig4 mRNA was detected in liver tissue isolated from wild-type C57BL/6 mice (+/+), while human VSIG4 mRNA was exclusively detected in homozygous B-hVSIG4 mice.

Protein Expression Analysis

Speciesspecific VSIG4 expression analysis in wild-type and humanized B-hVSIG4 mice. Peritoneal exudate macrophages (PEMs) were isolated from wild-type C57BL/6 (+/+) and homozygous B-hVSIG4 (H/H) mice and analyzed by flow cytometry using species-specific anti-VSIG4 antibodies. Human VSIG4 protein was exclusively detected in B-hVSIG4 mice compared to wild-type mice.

In Vivo Efficacy Evaluation of an Anti-Human VSIG4 Antibody

Anti-tumor activity of an anti-human VSIG4 antibody in humanized B-hVSIG4 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hVSIG4 (H/H) mice (female, 7-week-old, n=5), when the tumor volume reached approximately 100-150 mm3, mice were grouped and treated with isotype control or an anti-human VSIG4 antibody. (A) An anti-human VSIG4 antibody (hVSIG4 Ab-A, in house) slowed tumor growth in B-hVSIG4 mice compared to vehicle control, (B) without negatively impacting body weight changes. This data demonstrates that humanized B-hVSIG4 mice provide a powerful preclinical model for in vivo efficacy evaluation of anti-human VSIG4 antibodies. Values are expressed as mean ± SEM.

Analysis of tumor infiltrating lymphocytes

Analysis of tumor infiltrating lymphocytes (TILs) in humanized B-hVSIG4 mice. Tumor cells were harvested at the experimental endpoint (n=5), and analyzed by flow cytometry to assess lymphocyte cell number and proportion changes in humanized B-hVSIG4 mice treated with either isotype or anti-human VSIG4 antibodies. Percentages of CD8+ T cells, CD4+ T cells, Tregs, M1 macrophages and M1/M2 ratio were increased, while percentages of MDSCs and M2 macrophages were decreased in mice treated with an anti-VSIG4 antibody. Values are expressed as mean ± SEM.

References

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  3. Li, J., et al. VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism. Nat Commun 8, 1322 (2017).
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Poster

AACR 2022: Evaluating In Vivo Efficacy of Anti-VSIG4 Antibodies in Humanized B-hVSIG4 Mice