Preclinical humanized CD39 mouse model
The hCD39 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint CD39 in fully immunocompetent mice.
Design of the hCD39 mouse
The humanized CD39 model, developed by Knockin at the mouse CD39 locus, expresses a chimeric CD39 with a human extracellular and murine transmembrane and intracellular domains. The design also gives access to CD39 conditional Knockout mice.
The human CD39 expression recapitulates murine CD39 expression. hCD39 is functional: α-human CD39 specifically reduces human CD39 activity.
hCD39 features
- The CD39 extracellular domain is entirely humanized
- Physiological regulation and expression pattern of the human CD39
- Fully functional mouse immune system
- Lack of expression of the murine target gene, thus avoiding cross-reactivity
Validation
hCD39 expression pattern recapitulates mCD39
hCD39 and mCD39 expression on freshly isolated splenocytes on A) dendritic cells (CD3-CD19-CD11b+CD11c+), B) B cells (CD3-CD19+), and C) Tregs (viable, CD3+CD4+CD25+Foxp3+).
hCD39 is functional: anti-human CD39 specifically reduces human CD39 activity
Freshly isolated splenocytes from A) Wild-type and B) hCD39 mice, stimulated with anti-mCD39, anti-hCD39 or inhibitor control ARL (ectonucleotidases inhibitor) for 1h. ATP level was measured by CellTiter-Glo® luminescent cell assay following ATP addition. Results are expressed as mean±SD. Two-way ANOVA (**p<0.01; ***p<0.001; ****p<0.0001)
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Preclinical humanized CD39 mouse model
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