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B-hSIRPA mice
Strain Name C57BL/6-Sirpatm1(SIRPA)/Bcgen Common Name  B-hSIRPA mice
Background C57BL/6 Catalog number  110016
Aliases 
Sirpa (signal-regulatory protein alpha)

Gene Description


SIRPA (Signal-regulatory protein alpha) is a transmembrane protein widely expressed in myeloid cells , stem cells and neurons . Its extracellular part include 3 Immunoglobulinlike domains. SIRPα binds to its ligand CD47 through the variable IgV-like domains. CD47 is also widely expressed in multiple tissue cells. CD47+ cells activate SIRPα on macrophage surface to prevent its phagocytosis. Previous studies reveal that the diversity of SIRPα is the key to human hematopoietic stem cell suppression, especially tumor suppression. The interruption of SIRPα -CD47 interaction substantially inhibits a variety of tumors. SIRPα/CD47 antibodies are considered as the next star target for tumor immunosuppression following PD1/PD-L1 antibodies.


Protein Expression Analysis


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Abdominal cells from both wild type (WT) C57BL/6 and homozygous B-hSIRPA mice were analyzed by flow cytometry. Mouse SIRPα+ cells were detectable in non-T and non-B cells from both WT C57BL/6 and the homozygous B-hSIRPA mice, while human SIRPA+ cells were only detectable in non-T and non-B cells from the homozygous B-hSIRPA mice. This might result from the cross recognition of hSIRPA by anti-mSIRPA antibodies. 

Human SIRPA mAb efficacy evaluation (MC38-hCD47 cells)


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Murine colon cancer MC38-hCD47 cells (without mCD47 cells) were subcutaneously implanted into homozygous B-hSIRPA mice. Mice were grouped when the tumor size was approximately 150±50mm3 (n=5). Three human SIRPA antibodies differently inhibited tumor growth, confirming that the B-hSIRPA mouse model is a powerful tool for in vivo SIRPA antibody pharmacological efficacy study. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.