녹아웃(KO) 마우스 | Cyagen Korea

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Strain Background: C57BL/6N

 

Construction Strategy:

The humanized GITR mouse model (hPhGITR) is developed by knockin at the mouse VISTA locus and driven by the endogenous promoter. It expresses a chimeric GITR with a human extracellular and murin intracellular domain.

 

hGITR Features:

  •   hGITR expression displays physiological regulation and expression pattern
  •   Fully functional mouse immune system
  •   Lack of expression of the murine target gene, thus avoiding cross-reactivity

 

Research and Application:

The hGITR mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint (ICP) GITR in fully immunocompetent mice.

 

Validation Data:

Figure 1. hGITR expression is induced after stimulation. Expression of human GITR on αCD3/αCD28 stimulated splenocytes (2 days), analyzed by flow cytometry on Treg (CD4+ Foxp3+), conventional CD4 (CD4conv) T cell (CD3+CD4+), CD8 (CD3+CD8+) and B cells (CD3-CD19+).

Figure 2. hGITR is functional ex vivo in effector T cells and Tregs. Treg (CD4+Foxp3+) stimulated or not with mouse or human GITRL for 2h and then co-cultured with CD4conv T cells (CD4+CD25- ) labeled with CFSE and activated with aCD3 +/- human GITRL.

Figure 3. hGITR is induced on TILs. Isolating splenocytes and tumor-infiltrating lymphocytes (TILs) from hGITR mice with MB49 bladder cancer after MB49 injection, hGITR expression on Treg (CD4+Foxp3+), CD4conv (CD3+CD4+) and CD8 (CD3+CD8+).

Figure 4. In vivo anti-tumor effect in response to anti-hGITR mAb treatment. Wild-type and hGITR homozygous mice were respectively inoculated with MB49 bladder cancer cells, treatment with anti-hGITR inhibits tumor growth in hGITR homozygous mice.

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