B-hTREM1 mice

Basic Information

Gene Targeting Strategy

Exons 1~4 of the murine Trem1 gene, which encode the extracellular domain, were replaced by human TREM1 exons 1~4 in B-hTREM1 mice.

mRNA Expression Analysis

TREM1 gene expression analysis in wild type and humanized B-hTREM1 mice. Human TREM1 mRNA expression level in B-hTREM1 (H/H) mice was similar to murine Trem1 expression level in C57BL/6 (+/+), demonstrating that introduction of hTREM1 in place of its mouse counterpart does not change the overall expression level of TREM1 mRNA.

Protein Expression Analysis

Species-specific TREM1 expression analysis in humanized B-hTREM1 mice. Blood was collected from wild-type C57BL/6 (+/+) and heterozygous B-hTREM1 (H/+) mice and analyzed by flow cytometry using species-specific anti-TREM1 antibodies. Mouse TREM1 was detected in wild-type and heterozygous B-hTREM1 mice, while human TREM1 was exclusively detected in humanized B-hTREM1 mice.

Tumor Growth Curve and Body Weight Changes

Subcutaneous homograft tumor growth of MC38 cells in B-hTREM1 mice. Wild-type murine colon cancer MC38 cells (5×10⁵) were subcutaneously implanted into wild-type C57BL/6 mice and humanized B-hTREM1 mice (male, 8-week-old, n=6). Tumor volume and body weight were measured twice a week. (A) Average tumor volume ± SEM. (B) Body weight (Mean± SEM). Volume was expressed in mm³ using the formula: V=0.5 X long diameter X short diameter². Shown in panel A, MC38 cells were able to establish tumors in B-hTREM1 mice, which can be used for in vivo efficacy studies.

Combination therapy of an anti-mouse PD-1 antibody with an anti-human TREM1 antibody

Antitumor activity of anti-mouse PD-1 antibody combined with anti-human TREM1 antibody in B-hTREM1 mice. (A) Anti-mouse PD-1 antibody combined with anti-human TREM1 antibody inhibited MC38 tumor growth in B-hTREM1 mice. Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hTREM1 mice (female, 9-week-old, n=5). Mice were grouped when tumor volume reached approximately 80-100 mm3, at which time they were treated with mPD-1 and hTREM1 antibodies. (B) Body weight changes during treatment. As shown in panel A, combination of anti-hTREM1 and anti-mPD-1 antibody shows more inhibitory effects than individual groups, demonstrating that the B-hTREM1 mice provide a powerful preclinical model for in vivo evaluation of anti-human TREM1 antibody. Values are expressed as mean ± SEM.