Preclinical Double-Targeted hGITR/Foxp3 Reporter Mouse Model
Design of the hGITR/Foxp3 mouse
The humanized GITR/Foxp3 model was generated by intercrossing hGITR and Foxp3-IRES-mRFP (FIR) reporter mice.
The hGITR is developed by Knockin at the mouse GITR locus, and expresses a chimeric GITR with a human extracellular and murine intracellular domain. hGITR is regulated by the endogenous mouse promoter. The FIR's bicistronic reporter expressing a red fluorescent protein (RFP) has been knocked into the endogenous Foxp3 locus and faithfully mirrors Foxp3 expression.
Applications in immuno-oncology
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.
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hGITR/Foxp3 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 GITR, thus avoiding cross-reactivity
- Physiological expression of murine Foxp3
- RFP reporter faithfully mirrors Foxp3 expression
hGITR/Foxp3 validation*
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hGITR expression pattern in hGITR/Foxp3 mice recapitulates mGITR expression in wild-type mice Expression of human and mouse GITR on αCD3/αCD28-stimulated splenocytes (5 days), analyzed by flow cytometry on Tregs and conventional CD4+ (CD4conv) T cells. |
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RFP expression mirrors Foxp3 protein expression Expression of mRFP on non-permeabilized (A) or permeabilized (B) freshly isolated splenocytes (CD3+CD4+) from hGITR/Foxp3 mice. mRFP+ cells were sorted and permeabilized to allow Foxp3 detection (C). |
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Suppressive function of Treg is preserved Isolated CD4+CD25- Teff cells were labeled with CTV and cultured with various concentrations of isolated RFP+ Treg cells in presence of antigen-presenting cells treated with mitomycin and αCD3 for 4 days. Proliferation was assessed by flow cytometry (CTV+ cells) on viable cells. Results were analysed by Student t test *p<0.001. |
* For more validation data please consult our hGITR and Foxp3-IRES-mRFP (FIR) reporter mouse webpages, or contact us.
Ready to be shipped to your lab
- Cohorts available upon request
- Studies can be carried out at your site or at your favorite CRO
- SOPF certification and worldwide delivery by professional breeders
- Models provided with FTO on patent-protected technologies used for model generation
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Are you looking for another target? Follow this link humanized immune checkpoint (ICP) mouse models, or contact us. |