Basic Information
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Gene targeting strategy
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Gene targeting strategy for B-hTREM2 mice(C). Exons 1~5 and 3` UTR of the mouse Trem2 gene that encode the full-length protein were replaced by human TREM2 exons 1~5 and 3` UTR in B-hTREM2 mice(C).
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mRNA expression analysis
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Species-specific TREM2 gene expression analysis in wild-type and humanized B-hTREM2 mice(C) by RT-PCR. Murine Trem2 mRNA was detected in wild-type BALB/c (+/+) mice, while human TREM2 mRNA was detected in homozygous B-hTREM2 (H/H) mice(C).
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Protein expression analysis
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Species-specific TREM2 protein expression analysis in wild-type and humanized B-hTREM2 mice(C). Microglial cells were isolated from wild-type BALB/c (+/+) and homozygous B-hTREM2 (H/H) mice(C) and analyzed by flow cytometry using a cross-reactive anti-TREM2 antibody. TREM2 protein was detected in wild-type and B-hTREM2 mice(C).
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In vivo efficacy of anti-human TREM2 antibody
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Antitumor activity of anti-human TREM2 antibody in B-hTREM2 mice(C). (A) Anti-human TREM2 antibody inhibited EMT-6 tumor growth in B-hTREM2 mice(C). Murine breast carcinoma EMT-6 cells were subcutaneously implanted into homozygous B-hTREM2 mice(C) (female, 10 week-old, n=6). Mice were grouped when tumor volume reached approximately 50-80 mm3, and treated with anti-hTREM2 antibody at doses and schedules in panel A. (B) Body weight changes during treatment. As shown in panel A, anti-human TREM2 antibody (in house) were efficacious in controlling tumor growth in B-hTREM2 mice(C), demonstrating they provide a powerful preclinical model for in vivo evaluation of anti-human TREM2 antibody. Values are expressed as mean ± SEM.
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Summary
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- mRNA expression analysis
Mouse Trem2 mRNA was detectable in wild-type mice (+/+). Human TREM2 mRNA was detectable only in homozygous B-hTREM2 mice(C) but not in wild-type mice.
- Protein expression analysis
TREM2 was detectable in microglia of wild-type mice and homozygous B-hTREM2 mice(C).
- Anti-human TREM2 antibody (in house) were efficacious in controlling tumor growth in B-hTREM2 mice(C).
