• TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) are TREM1 and PGLYRP1 dual-gene humanized mice generated on a C57BL/6N background for inflammatory disease research.
• TREM1 is a myeloid receptor expressed on neutrophils, inflammatory monocytes, and tumor-associated macrophages, where it amplifies inflammatory signaling through DAP12/SYK and NF-κB pathways.
• PGLYRP1 is a peptidoglycan-recognition protein associated with innate immune responses and inflammatory regulation.
• TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) provide an in vivo platform for anti-human TREM1 antibody efficacy evaluation in DSS-induced acute colitis and related inflammation studies.

Key Advantages

• Human TREM1 expression validated in neutrophils and CD11b+ cells by flow cytometry
• Human soluble TREM1 expression validated in serum by ELISA after LPS stimulation
• Human PGLYRP1 expression validated in serum by ELISA with or without LPS stimulation
• Trem1 and Pglyrp1 humanization strategies preserve endogenous mouse promoter control while disrupting mouse gene transcription/translation
• DSS-induced acute colitis efficacy data available for anti-human TREM1 antibody treatment
• Supports research on innate immunity, myeloid inflammation, colitis, TREM1 antagonist, and inflammatory-factor studies

Validation

• TREM1 Protein Validation: Human TREM1 was detected in neutrophils and CD11b+ cells of homozygous TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) by flow cytometry.
• Soluble TREM1 Validation: Human soluble TREM1 was detected in serum from homozygous TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) by ELISA after LPS stimulation.
• PGLYRP1 Protein Validation: Human PGLYRP1 was detected in serum from homozygous TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) by ELISA.
• DSS Model Validation: TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) were used in a DSS-induced acute colitis model to evaluate anti-human TREM1 antibody efficacy.
• Inflammation Marker Validation: Serum pro-inflammatory factors mouse IL-6 and TNFα were measured after antibody treatment in DSS-induced colitis.

Application

• Anti-human TREM1 antibody efficacy evaluation
• DSS-induced acute colitis model studies
• Myeloid receptor and innate immune signaling research
• Inflammatory cytokine and serum biomarker analysis
• IBD and acute intestinal inflammation drug development
• Preclinical evaluation of TREM1-targeted biologics

In TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1), mouse Trem1 exons 1-4 encoding the signal peptide and extracellular domain were replaced by human counterparts, while the mouse transmembrane and cytoplasmic regions, promoter, 5’ UTR, and 3’ UTR were retained. Mouse Pglyrp1 exons 1-3 encoding the whole molecule, including the 3’ UTR, were replaced by human counterparts while the mouse promoter and 5’ UTR were retained. This strategy drives human TREM1 and PGLYRP1 expression under endogenous mouse regulatory elements and disrupts mouse Trem1 and Pglyrp1 transcription/translation.

Strain-specific analysis of mouse and human TREM1 protein expression in wild-type C57BL/6 mice and TREM1/PGLYRP1 humanized mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6 mice (+/+) and homozygous TREM1/PGLYRP1 humanized mice (H/H; H/H). Mouse and human TREM1 protein expression was analyzed by flow cytometry using species-specific anti-mouse TREM1 (R&D Systems, FAB1187P) and anti-human TREM1 (BioLegend, 314909) antibodies. Mouse TREM1 was detected in neutrophils and CD11b⁺ cells from wild-type C57BL/6 mice, whereas human TREM1 was detected in neutrophils and CD11b⁺ cells from homozygous TREM1/PGLYRP1 humanized mice but not in wild-type mice.

Strain-specific analysis of soluble mouse and human TREM1 protein expression in wild-type C57BL/6 mice and TREM1/PGLYRP1 humanized mice by ELISA. Serum samples were collected from wild-type C57BL/6 mice (+/+) and homozygous TREM1/PGLYRP1 humanized mice (H/H; H/H) following in vivo stimulation with lipopolysaccharide (LPS, 20 μg/mouse) for 2 hours. Soluble mouse TREM1 was detected in wild-type C57BL/6 mice, whereas soluble human TREM1 was detected in homozygous TREM1/PGLYRP1 humanized mice. These results suggest that mouse matrix metalloproteinases (MMPs) can cleave human TREM1, leading to the release of soluble human TREM1. ND: not detectable.

Strain-specific analysis of mouse and human PGLYRP1 protein expression in wild-type C57BL/6 mice and TREM1/PGLYRP1 humanized mice by ELISA. Serum samples were collected from wild-type C57BL/6 mice (+/+) and homozygous TREM1/PGLYRP1 humanized mice (H/H; H/H), with or without in vivo stimulation with lipopolysaccharide (LPS) for 2 hours. Mouse PGLYRP1 was detected in wild-type C57BL/6 mice, whereas human PGLYRP1 was detected in homozygous TREM1/PGLYRP1 humanized mice.

• The percentages of T cells, B cells, NK cells, dendritic cells (DCs), monocytes, macrophages, and neutrophils in homozygous TREM1/PGLYRP1 humanized mice were comparable to those in wild-type C57BL/6N mice.
• Humanization of TREM1 and PGLYRP1 did not alter normal immune cell development or distribution in the spleen.

Flow cytometry analysis of leukocyte subpopulations in immune organs and peripheral blood of TREM1/PGLYRP1 humanized mice. Splenocytes, peripheral blood, and lymph nodes were isolated from female wild-type C57BL/6N mice and TREM1/PGLYRP1 humanized mice (8 weeks old, n = 3). Single live cells were gated on the CD45⁺ population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM.

• The proportions of CD4⁺ T cells, CD8⁺ T cells, and regulatory T cells (Tregs) in homozygous TREM1/PGLYRP1 humanized mice were comparable to those in wild-type C57BL/6N mice.
• Humanization of TREM1 and PGLYRP1 did not alter normal T-cell development, differentiation, or distribution in the spleen.

Flow cytometry analysis of T-cell subpopulations in immune organs and peripheral blood of TREM1/PGLYRP1 humanized mice. Splenocytes, peripheral blood, and lymph nodes were isolated from female wild-type C57BL/6N mice and TREM1/PGLYRP1 humanized mice (8 weeks old, n = 3). Single live cells were gated on the CD3⁺ T-cell population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM.

Experimental schedule for establishing a DSS-induced acute colitis model in TREM1/PGLYRP1 humanized mice. Homozygous TREM1/PGLYRP1 humanized mice were divided into four groups. The normal control group received regular drinking water for 7 consecutive days, while the DSS-treated groups received drinking water containing 3.5% dextran sulfate sodium (DSS) for 7 consecutive days to induce acute colitis.

Anti-human TREM1 antibody ameliorates DSS-induced acute colitis in TREM1/PGLYRP1 humanized mice. TREM1/PGLYRP1 humanized mice received regular drinking water, 3.5% DSS, or 3.5% DSS plus TREM1-318-IgG1.3f at 10 or 25 mg/kg every 3 days (Q3D) for 7 days. (A) Body weight change. (B) Disease activity index (DAI) score. (C) Colon length and spleen index. (D) Representative colon images.

Anti-human TREM1 antibody improves colon histopathology in a DSS-induced acute colitis model using TREM1/PGLYRP1 humanized mice. TREM1/PGLYRP1 humanized mice received 3.5% DSS for 7 days with or without TREM1-318-IgG1.3f at 10 or 25 mg/kg every 3 days (Q3D). (A) Representative hematoxylin and eosin (H&E)-stained colon sections at 100× and 200× magnification. (B) Histopathological scores.

Anti-human TREM1 antibody improves colon histopathology in a DSS-induced acute colitis model using TREM1/PGLYRP1 humanized mice. TREM1/PGLYRP1 humanized mice received 3.5% DSS for 7 days with or without TREM1-318-IgG1.3f at 10 or 25 mg/kg every 3 days (Q3D). (A) Representative hematoxylin and eosin (H&E)-stained colon sections at 100× and 200× magnification. (B) Histopathological scores.

Anti-human TREM1 antibody reduces pro-inflammatory cytokine levels in a DSS-induced acute colitis model using TREM1/PGLYRP1 humanized mice. TREM1/PGLYRP1 humanized mice received 3.5% dextran sulfate sodium (DSS) for 7 days, with or without treatment with TREM1-318-IgG1.3f at 10 or 25 mg/kg every 3 days (Q3D). Serum IL-6 and TNF-α levels were measured on day 7 to assess systemic inflammatory responses.

Q1: What are TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1)?

TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) are TREM1 and PGLYRP1 dual-gene humanized mice on a C57BL/6N background, developed for innate immunity and inflammatory disease research.

Q2: Why are TREM1 and PGLYRP1 important?

TREM1 is an activating myeloid receptor that amplifies inflammatory signaling, while PGLYRP1 is associated with innate immune recognition and inflammatory regulation.

Q3: How was human TREM1 and PGLYRP1 validated in this model?

Human TREM1 was validated by flow cytometry in neutrophils and CD11b+ cells, soluble human TREM1 was validated by ELISA after LPS stimulation, and human PGLYRP1 was validated by ELISA in serum.

Q4: Can TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) be used for antibody efficacy studies?

Yes. TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1) have in vivo DSS-induced acute colitis efficacy data for anti-human TREM1 antibody treatment.

Q5: What are the main applications of TREM1/PGLYRP1 humanized mice (B-hTREM1/hPGLYRP1)?

Applications include anti-human TREM1 antibody evaluation, DSS-induced colitis studies, myeloid inflammation research, serum inflammatory-factor analysis, and inflammatory disease drug development.