Preclinical humanized GITR mouse model
The hGITR mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint GITR in fully immunocompetent mice.
Design of the hGITR mouse
The humanized GITR mouse model (hGITR) is developed by Knockin at the mouse GITR locus and driven by the endogenous promoter. It expresses a chimeric GITR with a human extracellular and murin intracellular domain. The human isoforms display diversity within the intracellular domain, and are expressed in case they support different signaling functions.
hGITR features
- The GITR extracellular domain is entirely humanized
- Physiological regulation and expression pattern of the human GITR
- Fully functional mouse immune system
- Lack of expression of the murine target gene, thus avoiding cross-reactivity
Validation
hGITR expression is induced after stimulation
Expression of human GITR on aCD3/aCD28-stimulated splenocytes (2 days), analyzed by flow cytometry on Tregs, conventional CD4 (CD4conv), CD8 and B cells.
In vivo anti-tumor effect in response to anti-hGITR mAb treatment
hGITR homozygous mice with MB49 bladder cancer at day 0 were treated with vehicle or ahGITR mAb on days 7, 10 and 13. Tumor growth was followed until day 30. Unpaired t-test statistics: * p<0.05, ** p<0.005.
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hGITR
hGITR/Foxp3
The hGITR/Foxp3 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint GITR. The red fluorescent protein regulated under the Foxp3 promoter allows you to efficiently monitor and sort Foxp3-expressing cells from different lymphocyte lineages and lymphoid organs.
Preclinical humanized GITR mouse model
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