Preclinical double-humanized GITR/GITRL mouse model
The hGITR/hGITRL mouse model enables in vivo efficacy assessment and profiling of agonist and antagonist antibodies targeting human immune checkpoint GITR and/or GITRL in fully immunocompetent mice.
Design of the hGITR/hGITRL mouse
The double-humanized GITR and GITRL mouse model (hGITR/hGITRL) was generated by intercrossing hGITR and hGITRL mice.
hGITR was developed by inserting, within the mouse GITR locus, a chimeric GITR with the human extracellular and the murine intracellular domain.
hGITRL was generated by inserting, within the mouse GITRL locus, a chimeric GITRL with the human extracellular and the murine intracellular domain.
Both hGITR and hGITRL expressions are regulated by endogenous mouse promoters.
hGITR/hGITRL features
- GITR and GITRL extracellular domains are entirely humanized
- hGITR and hGITRL expression driven by the respective endogenous mouse promoter
- Preservation of the target-ligand interaction
- Fully functional mouse immune system
- Lack of expression of the murine target gene, thus avoiding cross-reactivity
Validation
hGITR-Fc significantly inhibits ear swelling at 24 and 48 hours post DNFB challenge in hGITR/hGITRL mice
Mice were injected with vehicle, IgG, GITR-Fc or mCTLA4-Ig on day -1, sensitized with DNFB on day 0, and then challenged on the ear on day 5. The mean ear-swelling response was determined at 24 and 48 hours post DNFB challenge.
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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 double-humanized GITR/GITRL mouse model
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