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B-hSIRPA mice

2017-05-09 17:40:28.0

Strain description

Strain NameC57BL/6-Sirpatm1(hSIRPA)/BcgenCommon NameB-hSIRPA mice
BackgroundC57BL/6Catalog numberB-CM-030
Catalog number (Males)BCM030MCatalog number (Females)BCM030F
Related GenesSirpa (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 includes 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 PD-1/PD-L1 antibodies.

 

Targeting strategy

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mRNA expression analysis

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Fig 1. RT-PCR analysis of the SIRPA gene.

The mSIRPA mRNA was detected in wild t ype C57BL/6, while the hSIRPA mRNA was detected in the homozygous B-hSIRPA mice.



Protein expression analysis

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Fig 2. Splenocytes from both wild type (WT) C57BL/6 and the B-hSIRPA heterozygous mice were analyzed by flow cytometry. 

Mouse SIRPα+ cells were detected in non-T and non-B cells from both WT C57BL/6 and the homozygous B-hSIRPA mice, while human SIRPα+ cells were only detected 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.




SIRPA Abs efficacy evaluation

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Fig 3. Murine colon cancer MC38-hCD47 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 studies. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.



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