B-hTNFA/hTNFR2 mice

C57BL/6-Tnftm1(TNF)Bcgen Tnfrsf1btm1(TNFRSF1B)Bcgen/Bcgen • 120749

B-hTNFA/hIL23A/hIL12B mice
B-hTNFA/hTNFR2/hTNFR1 mice

B-hTNFA/hTNFR2 mice

Product nameB-hTNFA/hTNFR2 mice
Catalog number120749
Strain nameC57BL/6-Tnftm1(TNF)Bcgen Tnfrsf1btm1(TNFRSF1B)Bcgen/Bcgen
Strain backgroundC57BL/6
AliasesNF (DIF-alpha, TNFA, TNFSF2, TNLG1F, TNF) TNFRSF1B (CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B, TNFR2, TNFR80, p75, p75TNFR)

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  • Targeting strategy
  • Phenotypic analysis
  • Efficacy

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    Publication

      Targeting strategy

      Gene targeting strategy for B-hTNFA/hTNFR2 mice. The targeted mouse Tnf whole genomic sequence was replaced by human TNF whole genomic sequence in B-hTNFA/hTNFR2 mice. The exons 2~6 of mouse Tnfr2 gene that encode the extracellular domain was replaced by human TNFR2 exons 2~6 in B-hTNFA/hTNFR2 mice.

      mRNA expression analysis

      Strain specific analysis of TNFA and TNFR2 gene expression in WT and B-hTNFA/TNFR2 mice by RT-PCR. Mouse Tnfα and Tnfr2 mRNA were detectable only in splenocytes of wild-type (+/+) mice. Human TNFA and TNFR2 mRNA were detectable only in B-hTNFA/hTNFR2 mice, but not in WT mice.

      Protein expression analysis

      Strain specific TNFα expression analysis in homozygous B-hTNFA/hTNFR2 mice by ELISA.Serum were collected from WT and homozygous B-hTNFA/hTNFR2 (H/H) mice stimulated with LPS in vivo, and analyzed by ELISA with species-specific TNFα ELISA kit. Mouse TNFα was detectable in WT mice. Human TNFα was exclusively detectable in homozygous B-hTNFA/hTNFR2 but not WT mice.

      Strain specific TNFR2 expression analysis in homozygous B-hTNFA/hTNFR2 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hTNFA/hTNFR2 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-TNFR2 antibody. Mouse TNFR2 was detectable in WT mice. Human TNFR2 was exclusively detectable in homozygous B-hTNFA/hTNFR2 but not WT mice.

      Strain specific TNFR2 expression analysis in homozygous B-hTNFA/hTNFR2 mice by flow cytometry. Splenocytes were collected from WT and homozygous B-hTNFA/hTNFR2 (H/H) mice stimulated with anti-CD3ε in vivo, and analyzed by flow cytometry with species-specific anti-TNFR2 antibody. Mouse TNFR2 was detectable in WT mice. Human TNFR2 was exclusively detectable in homozygous B-hTNFA/hTNFR2 mice but not in WT mice.

      In vivo efficacy of anti-human TNFR2 antibody
      Anti-tumor activity of anti-human TNFR2 antibody in B-hTNFA/hTNFR2 mice. (A) Anti-human TNFR2 antibody get from cooperation company inhibited MC38 tumor growth in B-hTNFA/hTNFR2 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hTNFA/hTNFR2 mice (female, 7-week-old). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human TNFR2 antibody. (B) Body weight changes during treatment. As shown in panel A, anti-human TNFR2 antibody was efficacious in controlling tumor growth in B-hTNFA/hTNFR2 mice. B-hTNFA/hTNFR2 mice provide a powerful preclinical model for in vivo evaluation of anti-human TNFR2 antibody. Values are expressed as mean ± SEM.