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B-hPD1/hLAG3/hTIM3 mice
Strain Name C57BL/6-Pdcd1tm1(PDCD1)Lag3tm1(LAG3)Havcr2tm1(HAVCR2)/Bcgen Common Name  B-hPD1/hLAG3/hTIM3 mice
Background C57BL/6 Catalog number  130999
Aliases 
PDCD1: PD-1; LAG3: CD223; HAVCR2: TIM3
Gene description

PD-1 (Programmed death-1) is mainly expressed on the surface of T cells and primary B cells. The two PD-1 ligands, PD-L1 and PD-L2, are widely expressed on antigen-presenting cells (APCs). PD-1 interacts with its ligands and plays an important role in the negative regulation of the immune response. PD-L1 protein expression is detected in many human tumor tissues. PD-L1 expression in tumor cells could be induced by the microenvironment of tumor cells. PD-L1 expression is favorable for tumorigenesis and growth, for induction of anti-tumor T Cell apoptosis, and for escaping responses by the immune system. Inhibition of PD-1 binding to its ligand can result in tumor cells that are exposed to the killing version of the immune system, and thus is a target for cancer treatments.
LAG3 (Lymphocyte activation gene 3, CD223) is a lymphocyte activation gene and a member of the Ig family. It is mainly expressed in activated T cells, NK cells, B cells and plasmacytoid DCs. LAG3 is a negative regulator of immunity and mainly binds to MHC class Ⅱ molecules to regulate the function of dendritic cells. The expression of LAG3 is associated with the negative immunoregulatory function of specific T cells. Inhibition of LAG3 function enhances the antitumor effect of specific CD8+ T cells, therefore LAG3 is a potential target for tumor immunotherapy.

TIM3 (T-cell immunoglobulin domain and mucin domain-3) is an activation-induced inhibitory molecule involved in immune tolerance and T-cell exhaustion in chronic viral infection and cancers. TIM3 maturation and cell surface expression is facilitated by forming a heterodimeric interaction with CD66a. Co-blockade of CD66a and TIM3 enhanced anti-tumor immune responses, and eliminated tumors in mouse colorectal cancer models.


Protein expression analysis


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Strain specific PD-1, LAG3 and TIM3 expression analysis in homozygous B-hPD-1/hLAG3/hTIM3 mice by flow cytometry. 

Splenocytes from both wild type (+/+) C57BL/6  and  homozygous B-hPD-1/hLAG3/hTIM3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry. Mouse PD-1+ and TIM3+ T cells were only detectable in the WT C57BL/6 mice, human PD-1+, TIM3+ and LAG3+ T cells were only detectable in the homozygous B-hPD-1/hLAG3/hTIM3 mice. Mouse LAG3+ T cells were detectable in WT and homozygous B-hPD-1/hLAG3/hTIM3 mice, as the anti-mLAG3 antibody cross reacts with hLAG3. 


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Strain specific PD-1, LAG3 and TIM3 expression analysis in homozygous B-hPD-1/hLAG3/hTIM3 mice by flow cytometry. Splenocytes from both wild type (+/+) C57BL/6  and  homozygous B-hPD-1/hLAG3/hTIM3 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry. Mouse PD-1+ and TIM3+ T cells were only detectable in the WT C57BL/6 mice, human PD-1+, TIM3+ and LAG3+ T cells were only detectable in the homozygous B-hPD-1/hLAG3/hTIM3 mice. Mouse LAG3+ T cells were detectable in WT and homozygous B-hPD-1/hLAG3/hTIM3 mice, as the anti-mLAG3 antibody cross reacts with hLAG3. 


Analysis of spleen leukocytes cell subpopulations in B-hPD1/hLAG3/hTIM3 mice

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Analysis of spleen leukocyte subpopulations by FACS
Splenocytes were isolated from female C57BL/6 and B-hPD-1/hLAG3/hTIM3 mice (n=3, 6-week-old). Flow cytometry analysis of the splenocytes was performed to assess leukocyte subpopulations. A. Representative FACS plots. Single live cells were gated for CD45 population and used for further analysis as indicated here. B. Results of FACS analysis. Percent of T cells, B cells, NK cells, monocytes, Dendritic cells, granulocytes and macrophages in homozygous B-hPD-1/hLAG3/hTIM3 mice were similar to those in the C57BL/6 mice, demonstrating that introduction of hPD-1,hLAG3 and hTIM3 in place of its mouse counterpart does not change the overall development, differentiation or distribution of these cell types in spleen. Values are expressed as mean ± SEM.