Humanized TNF-α mouse model
The hTNF-α model provides new opportunities for assessment of anti-TNF therapies.
Design of the hTNF-α mouse model
TNF-α, a proinflammatory cytokine produced by macrophages and other cell types, is implicated in many autoimmune diseases. The humanized TNF-α model was developed by Knockin at the murine Tnf locus. The model expresses humanized TNF-α. Human TNF-α is driven by the murine Tnf endogenous promoter, allowing physiological conservation of TNF-α expression regulation and pattern.
hTNF-α features
- Humanization by gene substitution; the murine TNF-α gene is inactivated and replaced by the human TNF-α genomic portion
- Human TNF-α expression is driven by the mouse TNF-α endogenous promoter (physiological TNF-α regulation and expression pattern)
- Physiological expression level of human TNF-α
- No expression of murine TNF-α
- No physiological deregulation reported
Validation
hTNF-α homozygotes produce hTNF-α upon activation, but not mTNF-α
ELISA-based expression analysis of human (red) and murine (blue) TNF-α in: left panel) αCD3/αCD28-stimulated human PBMCs; and right panel) wild-type or humanized TNF-α (hTNF-α) mouse splenocytes activated (Act) or not (NA) with αCD3/αCD28. Unpaired T test **p<0.02
Antiproliferative activity of hTNF-α from humanized TNF-α mice
Supernatant from anti-CD3/anti-CD28-stimulated wild-type (blue) or humanized TNF-α (red) mouse splenocytes exerts dose-dependent antiproliferative activity on L929 cells (left panel). An effect partially blocked by preincubation (100 ng/mL, 2h) with anti-murine (clone TN3-19.12) or anti-human (clone Mab1) TNF-α neutralizing antibodies (right panel).
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