녹아웃(KO) 마우스 | Cyagen Korea

humanized TNF-α Mouse


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Strain Background: C57BL/6N

 

Model Features:

  •   Humanization by gene substitution; the murine TNF-α gene is inactivated and replaced by the human TNF-α genomic portion.
  •   The humanized TNF-α mouse model expresses human TNF-α but does not express murine TNF-α (Fig. 1A). Human TNF-α is driven by the endogenous promoter of mouse TNF-α, and its expression in mice has a normal physiological expression and regulation pattern.
  •   Physiological expression level of human TNF-α (Fig. 1B)

 

Research & Application:

The humanized TNF-α mouse model allows in vivo efficacy and safety assessment of anti-human TNF-α compounds in the field of autoimmune diseases and inflammation.

 

Validation Data:

Figure 1. Mean plasmatic concentrations of murine TNF-α and human TNF-α following LPS injection. Mean concentrations of murine TNF-α (A) and human TNF-α (B) measured by ELISA from plasma samples collected from WT (n=2) and KI (n=2) mice treated with saline solution vs. LPS.

Figure 2. ELISA analysis of humanized (red) and murine (blue) TNF-α expression. (Left) αCD3/αCD28 stimulated human peripheral blood mononuclear cells (hPMBC0 and (Right) wild-type or humanized TNF-α (hTNF-α) mouse spleen cells activated with αCD3/αCD28 (Act) or untreated (NA). After stimulated by αCD3/αCD28, humanized mouse peripheral blood mononuclear cells secrete humanized TNF-α (hTNF-α) instead of murine TNF-α (mTNF-α).

Figure 3. Humanized TNF-α (hTNF-α) and mouse TNF-α (mTNF-α) anti-proliferative activity. (Left) The supernatant of wild-type (mTNF-α) and hTNF-α mouse spleen cells activated by αCD3/αCD28 was collected to treat L929 cells. Compared with the supernatant of WT spleen cells, the supernatant of hTNF-α mice spleen cells used to treat L929 cells showed a concentration-dependent anti-proliferative phenotype of TNF-α. (Right) Pretreatment of wild-type mouse and hTNF-α mouse supernatants with murine and human TNF-α antibodies can relieve the inhibitory effect on L929 proliferation.

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