B-hTREM2 mice

Basic Information

Gene targeting strategy

Gene targeting strategy for B-hTREM2 mice. The exons 1~5 and 3` UTR of mouse Trem2 gene that encode the full-length protein were replaced by human TREM2 exons 1~5 and 3` UTR in B-hTREM2 mice.

mRNA expression analysis

Species-specific TREM2 gene expression analysis in wild-type and humanized B-hTREM2 mice by RT-PCR. Murine Trem2 mRNA was detected in wild-type (+/+) mice, while human TREM2 mRNA was detected in homozygous B-hTREM2 (H/H) mice.

Protein expression analysis

Species-specific TREM2 protein expression analysis in wild-type and humanized B-hTREM2 mice. Brain tissue was isolated from wild-type (+/+) and heterozygous B-hTREM2 (H/+) mice and analyzed by western blot using an anti-hTREM2 antibody. Human TREM2 protein was detected in heterozygous B-hTREM2 mice.

In vivo efficacy of an anti-human TREM2 antibody

Anti-tumor activity of an anti-human TREM2 antibody in humanized B-hTREM2 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hTREM2 mice (male, 6-7-week-old, n=6). Mice were grouped when the tumor volume reached ~100 mm³, at which time the mice were treated with either an isotype control or an anti-human TREM2 antibody at doses and schedules as indicated. (A) Anti-human TREM2 antibody controlled MC38 tumor growth in B-hTREM2 mice, (B) without negatively impacting body weight changes. Values are expressed as mean ± SEM.

Poster

AACR 2023: Generation of Humanized TREM2 Mice for Preclinical Evaluation of Therapeutics Targeting Tumor-Associated Macrophages