Preclinical Double-Targeted hGITR/Foxp3 Reporter Mouse Model

Humanized Immune Checkpoint Mouse Models

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.

 

Request a quote here to get pricing, offers and hGITR/Foxp3 model information by phone or email.

 

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*

hGITR+Foxp3 ICP model validation 1

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.

hGITR+Foxp3 ICP model validation 2

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).

hGITR+Foxp3 ICP model validation 3

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
  • VAF Elite/SOPF certification and worldwide delivery by professional breeders
  • Models provided with FTO on patent-protected technologies used for model generation

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