Basic Information

Strain Name
C57BL/6-Sirpatm1(SIRPA)Cd47tm1(CD47)Il2rgtm1/Bcgen
Stock Number
130566
Common Name
B-hSIRPA/hCD47,Il2rg KO mice
Background
C57BL/6
Related Genes
BIT, CD172A, MFR, MYD-1, P84, PTPNS1, SHPS1, SIRP, IAP, MER6, OA3,  IL-2RG, IMD4, P64, SCIDX, SCIDX1

Description

Signal regulatory protein α (SIRPα) is a transmembrane protein with an extracellular region comprising three Ig-like domains and a cytoplasmic region containing immunoreceptor tyrosine-based inhibition motifs which mediate binding of the protein tyrosine phosphatases SHP1 and SHP2. SIRPα is especially abundant in myeloid cells such as macrophages and dendritic cells(DC), whereas it is expressed at very low levels in T, B ,NK, and NK T cells. SIRPα inhibits phagocytosis in macrophages upon interacting with its ligand CD47, which is commonly upregulated on the surface of malignant cells. Thus, antibodies that block the CD47-SIRPα interaction should enhance macrophage phagocytosis in the tumor microenvironment and inhibit tumor growth, making anti-SIRPα antibodies promising tools for cancer immunotherapy.

Biocytogen has developed the B-hSIRPA/hCD47,Il2rg KO mice. Il2rg gene was knocked out, while the mouse extracellular domain of Sirpa and CD47 genes were replaced with the extracellular domain of human SIRPα and CD47 genes. B cells, T cells and NK cells were decreased in B-hSIRPA/hCD47,Il2rg KO mice.

Details

Protein expression analysis

Species specific SIRPα expression analysis in B-hSIRPA/hCD47,Il2rg KO mice by flow cytometry. Splenocytes isolated from C57BL/6 (+/+) mice and homozygous B-hSIRPA/hCD47,Il2rg KO mice (H/H) stimulated with or without anti-mCD3ε in vivo and were analyzed by flow cytometry with anti-SIRPα antibodies. Human SIRPα was exclusively detectable in homozygous B-hSIRPA/hCD47,Il2rg KO mice but not in C57BL/6 mice. Mouse SIRPα was detectable in C57BL/6 and homozygous B-hSIRPA/hCD47,Il2rg KO mice, indicating that this anti-mouse SIRPα antibody was cross-reacting with human SIRPα.

Species specific CD47 expression analysis in B-hSIRPA/hCD47,Il2rg KO mice by flow cytometry. Splenocytes were isolated from C57BL/6 (+/+) mice and homozygous B-hSIRPA/hCD47,Il2rg KO mice (H/H) stimulated with or without anti-mCD3ε in vivo and were analyzed by flow cytometry with anti-CD47 antibodies. Mouse CD47 was only detectable in C57BL/6 mice. Human CD47 was exclusively detectable in homozygous B-hSIRPA/hCD47,Il2rg KO mice but not in C57BL/6 mice. Mouse and human CD47 were not detectable on T cells when stimulated with anti-mCD3ε antibody.