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B6-hCD47 Mouse
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B6-hCD47 Mouse
製品名
B6-hCD47 Mouse
製品ID
C001419
系統名
C57BL/6JCya-Cd47em1(hCD47)/Cya
背景情報
C57BL/6JCya
状況
このマウス系統を論文で使用する場合は、「B6-hCD47 Mouse(カタログ番号C001419)はサイアジェンから購入しました。」と引用してください。
Tumor Target Humanized Mouse Models
Immune Target Humanized Mouse Models
製品タイプ
年齢
遺伝子型
性別
数量
標準的な配送方法では、少なくとも3匹のヘテロ接合体キャリアを保証しています。ホモ接合体キャリアや指定された性別の個体の繁殖サービスも利用可能です。
お見積もりについてはこちらまでご連絡ください
Tumor Target Humanized Mouse Models
Immune Target Humanized Mouse Models
基本情報
検証 Data
関連リソース
基本情報
遺伝子名
遺伝子別名
IAP, OA3, MER6
NCBI ID
染色体
Chr 3
MGI ID
さらに
系統詳細
CD47, also known as Integrin Associated Protein (IAP), is a transmembrane protein that belongs to the immunoglobulin superfamily. It is widely expressed on the surface of almost all normal cells and is highly expressed in tumor cells [1].
SIRPα, a signal regulatory protein mainly expressed on macrophages, inhibits their phagocytosis of target cells by transmitting inhibitory signals when binding to CD47 on other cells. However, some tumor cells can evade phagocytosis and cause tumor immune escape by highly expressing CD47 and binding to SIRPα on macrophages, sending a “don’t eat me” signal. Targeting CD47 antibodies can initiate anti-tumor T cell immune responses and promote cancer-specific lymphocyte activation through macrophage-mediated phagocytosis of tumors. As a result, the CD47-SIRPα signaling pathway has great therapeutic potential and is a highly competitive target in tumor immunotherapy after PD-1/PD-L1 [1-2].
CD47 is a transmembrane protein with its extracellular domain serving as the receptor/ligand binding region and its intracellular domain responsible for signal transduction [3]. B6-hCD47 mice are obtained by replacing the fragment encoding the extracellular domain of CD47 protein in the mouse Cd47 gene with the corresponding human CD47 gene sequence, resulting in a model expressing the extracellular domain of human CD47 protein and the intracellular domain of mouse CD47 protein. This ensures normal binding with human antibodies and other protein drugs while completely retaining the intracellular part of mouse CD47 protein, maintaining normal intracellular signal transduction. B6-hCD47 mice can successfully express human CD47 protein and can be used for research on CD47-targeted inhibitors or antibody drug development and screening, pharmacology and safety evaluation, tumor immunotherapy evaluation, and mechanisms of tumor immune escape systems.
参考文献
Logtenberg MEW, Scheeren FA, Schumacher TN. The CD47-SIRPα Immune Checkpoint. Immunity. 2020 May 19;52(5):742-752.
Jiang Z, Sun H, Yu J, Tian W, Song Y. Targeting CD47 for cancer immunotherapy. J Hematol Oncol. 2021 Oct 30;14(1):180.
Barclay AN, Van den Berg TK. The interaction between signal regulatory protein alpha (SIRPα) and CD47: structure, function, and therapeutic target. Annu Rev Immunol. 2014;32:25-50.
系統作製戦略
The sequence encoding the extracellular domain of the mouse Cd47 gene was replaced with the sequence encoding the extracellular domain of the human CD47 gene.

Figure 1. Diagram of the gene editing strategy for the generation of B6-hCD47 mice.
適用分野
Development and screening of targeting CD47 inhibitors/antibody drugs;
Evaluation of the efficacy and safety of targeting CD47 inhibitors/antibodies;
Evaluation of tumor immunotherapy and research on tumor immune escape mechanisms.
検証 Data
1. The expression of mouse CD47 and human CD47
Peripheral blood (PB), thymus, spleen, and lung tissues from B6-hCD47 and wild-type mice were analyzed by flow cytometry to detect the expression of mouse and human CD47. Results showed that B6-hCD47 mice expressed high levels of human CD47 and almost no mouse CD47, indicating successful humanization of the mouse Cd47 gene.

Figure 2. Detection of mouse CD47 and human CD47 expression in B6-hCD47 Mice and wild-type (WT) mice.
2. Binding ability of B6-hCD47 mouse erythrocytes to Anti-CD47 antibody
All different CD47 antibodies can bind to the red blood cells (RBCs) of B6-hCD47 mice at high concentrations, among which B6H12 and antibody 2 show a relatively high binding level.

Figure 3. Binding of different antibodies to red blood cells (RBCs) from B6-hCD47 mice at the highest concentration (5000 ng/ml)*.
*The data are from a third-party customer. Both antibody 1 and antibody 2 are human CD47 antibodies, and B6H12 is a monoclonal antibody specific to human CD47 protein.
3. Binding strength of B6-hCD47 mouse erythrocytes to Anti-CD47 antibody
The data show that the average fluorescence intensity of B6-hCD47 mouse erythrocytes binding to various sources of human CD47 antibody increases as the antibody concentration increases. In contrast, the fluorescence intensity of binding to the non-CD47 antibody remains at 0, indicating no binding.

Figure 4. Average fluorescence intensity of B6-hCD47 mouse erythrocytes bound to antibodies*.
*Data comes from the Cyagen customer, where antibody 1 and antibody 2 are preclinical human CD47 antibodies.
4. Anti-CD47 antibody induces an agglutination reaction in erythrocytes of B6-hCD47 mice
The data show high concentrations of Antibody 1 and Antibody 2 can significantly induce erythrocyte agglutination in B6-hCD47 mice.

Figure 5. Agglutination reaction induced by different antibodies to erythrocytes of B6-hCD47 mice*.
*Data comes from the Cyagen customer, where both antibody 1 and antibody 2 are preclinical human CD47 antibodies, and B6H12 is a monoclonal antibody specific to the human CD47 protein.
関連リソース
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