B-hSIGLEC8 mice

C57BL/6-Gt(ROSA)26tm1(SIGLEC8)Bcgen/Bcgen • 111149

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B-hSIGLEC8 mice

Catalog Number: 111149
Strain Name: C57BL/6-Gt(ROSA)26tm1(SIGLEC8)Bcgen/Bcgen
Strain Background: C57BL/6
NCBI gene ID: 27181 (Human)
Aliases: SAF2; SIGLEC-8; SIGLEC8L
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B-hSIGLEC8 mice

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  • Description
  • Targeting strategy
  • Phenotypic analysis
  • Efficacy
  • FAQ section

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      Description
      • B-hSIGLEC8 mice are human SIGLEC8 transgenic mice generated on a C57BL/6 background for eosinophil and mast cell research.
      • SIGLEC8 is an inhibitory receptor expressed on human eosinophils and mast cells, making SIGLEC8 a relevant target for allergic inflammation and asthma-related drug discovery.
      • Human SIGLEC8 expression in B-hSIGLEC8 mice can be analyzed in eosinophils and peritoneal lavage mast cells by flow cytometry.
      • B-hSIGLEC8 mice support in vivo evaluation of anti-human SIGLEC8 antibodies, including lirentelimab-like benchmark antibodies, in asthma-like inflammation models.

      Key Advantages

      • Human SIGLEC8 transgenic mouse model on a C57BL/6 background
      • Human SIGLEC8 expression validated in eosinophils and mast cells by flow cytometry
      • BALF immune-cell changes evaluated in an asthma-like model
      • Useful for anti-human SIGLEC8 antibody efficacy, eosinophil biology, and allergic inflammation research

      Validation

      • Protein Validation: Human SIGLEC8 was detected in eosinophils and peritoneal lavage mast cells of homozygous B-hSIGLEC8 mice by flow cytometry.
      • Antibody-Binding Validation: Eosinophils and peritoneal lavage mast cells from B-hSIGLEC8 mice bound the anti-human SIGLEC8 benchmark antibody lirentelimab.
      • BALF Immune-Cell Validation: BALF immune cells were analyzed in B-hSIGLEC8 mice after PBS or lirentelimab treatment in an asthma-like model.
      • Histology Validation: H&E staining showed reduced eosinophil infiltration after lirentelimab treatment in the B-hSIGLEC8 asthma-like model.

      Application

      • Anti-human SIGLEC8 antibody efficacy evaluation
      • Asthma-like inflammation model studies
      • Eosinophil and mast cell biology research
      • Allergic inflammation and airway inflammation studies
      • Lirentelimab-like antibody binding and pharmacology studies
      • Preclinical respiratory inflammation model development
      Targeting strategy

      In B-hSIGLEC8 mice, a BAC containing the whole sequence of the human SIGLEC8 gene was inserted into the Rosa26 locus. This targeting strategy enables human SIGLEC8 expression in relevant immune-cell populations in a C57BL/6 background, supporting anti-human SIGLEC8 antibody binding and efficacy studies in eosinophil-, mast cell-, and asthma-related models.

      Human SIGLEC8 Expression Analysis

      Human SIGLEC8 expression analysis in homozygous B-hSIGLEC8 mice by flow cytometry. Blood and peritoneal lavage fluid were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hSIGLEC8 mice (H/H), and analyzed by FACS with anti-SIGLEC8 antibody. Human SIGLEC8 was detectable in eosinophils (88%, mSiglec-F+, mCD11c-) and mast cells (99.8%, mFcεRIα+, mCD117(c-kit)+, CD11b-) in homozygous B-hSIGLEC8 mice.

      Anti-Human SIGLEC8 Antibody Binding to Eosinophils and Mast Cells

      Analysis of eosinophils and mast cells of B-hSIGLEC8 mice by flow cytometry. Eosinophils and peritoneal lavage mast cells were isolated from wild-type C57BL/6 mice (+/+) and B-hSIGLEC8 mice (H/H). Flow cytometry analysis was performed to assess human SIGLEC8 expression using the benchmark antibody Lirentelimab (in house). Eosinophils were gated from the mSiglec-F+, mCD11c- population, and mast cells were gated from the CD45+mFcεRIα+, mCD117(c-kit)+CD11b- population. Lirentelimab binding was observed in homozygous B-hSIGLEC8 mice but not in wild-type mice.

      BALF Immune Cells in Mouse Asthma Model

      The number of BALF immune cells in mouse asthma model. BALF immune cells were isolated from B-hSIGLEC8 mice (n=6). The number of eosinophils was analyzed by flow cytometry under PBS or lirentelimab (in house) treatment. After lirentelimab treatment, the expression level of inflammatory cells was lower than the positive control in homozygous B-hSIGLEC8 mice.

      In Vivo Efficacy of Anti-Human SIGLEC8 Antibody

      H&E staining in asthma-like model in B-hSIGLEC8 mice. Lung tissues were collected at the study endpoint. H&E staining showed that lung tissues from B-hSIGLEC8 mice exposed to PBS aerosols did not show inflammation. OVA exposure resulted in a significant increase in peribronchial and perivascular inflammation in B-hSIGLEC8 mice. A significant reduction in eosinophil infiltration was observed in mice treated with lirentelimab (in house). Note: Lirentelimab in the treatment model group was administered via intratracheal aerosolization.

      FAQ section

      Q1: What are B-hSIGLEC8 mice?

      B-hSIGLEC8 mice are gene-humanized mice developed by Biocytogen for human target expression, pharmacology studies, and preclinical efficacy evaluation.

      Q2: Why are B-hSIGLEC8 mice useful?

      B-hSIGLEC8 mice support studies of human SIGLEC8 biology in eosinophils and mast cells, especially in allergic inflammation and asthma-like models.

      Q3: How was human SIGLEC8 expression validated?

      Human SIGLEC8 expression and lirentelimab binding were validated in eosinophils and peritoneal lavage mast cells by flow cytometry.

      * When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [B-hSIGLEC8 mice] (Cat# 111149) was purchased from Biocytogen.