Basic Information
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Gene targeting strategy
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Gene targeting strategy. The full coding region of mouse Plau was replaced by human PLAU coding region sequences in B-hPLAU/hPLAUR mice. The coding region except signal peptide of mouse Plaur gene was replaced by human PLAUR counterpart gene sequences in B-hPLAU/hPLAUR mice.
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Protein expression analysis
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Species-specific PLAU protein expression analysis in homozygous B-hPLAU/hPLAUR mice by ELISA. Serum was collected from wild-type C57BL/6 mice and homozygous B-hPLAU/hPLAUR mice (male, 9-week-old, n=3), and analyzed by ELISA with species-specific PLAU ELISA kits. Mouse PLAU were detectable in wild-type C57BL/6 mice. Human PLAU was exclusively detectable in homozygous B-hPLAU/hPLAUR mice but not in wild-type mice.
Species-specific PLAUR protein expression analysis in homozygous B-hPLAU/hPLAUR mice by flow cytometry. Bone marrow cells were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hPLAU/hPLAUR mice (H/H), and analyzed by flow cytometry with species-specific anti-PLAUR antibodies. Mouse PLAUR was only detected in dendritic cells from wild-type mice, while human PLAUR protein was detected in mono/macrophages, granulocytes, and dendritic cells from B-hPLAU/hPLAUR mice.
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In vivo efficacy of anti-PLAUR antibodies
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Antitumor activity of anti-PLAUR antibodies in B-hPLAU/hPLAUR mice bearing B-hPLAUR MC38 cells. (A) Tumor growth in B-hPLAU/hPLAUR mice that treated with anti-PLAUR antibodies (in house) indicated in the panel. (B) Body weight changes during treatment. Murine colon cancer MC38 cells that express the human PLAUR protein were subcutaneously implanted into homozygous B-hPLAU/hPLAUR mice (female, 7-9 week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with antibodies. Values are expressed as mean ± SEM.
Antitumor activity of anti-PLAUR antibodies in B-hPLAU/hPLAUR mice bearing B-hPLAUR MC38 cells. Tumor growth curve in individual B-hPLAU/hPLAUR mice that treated with anti-PLAUR antibodies (in house) indicated in the panel.
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Binding assay of anti-PLAUR antibodies with B-hPLAU/hPLAUR mice
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Analysis the binding of anti-human PLAUR antibodies with B-hPLAU/hPLAUR mice by flow cytometry. Macrophages in ascites of B-hPLAU/hPLAUR mice were performed to assess anti-human PLAUR antibodies (in house) binding. Both antibodies bind well with human PLAUR in homozygous mice.
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Summary
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Protein expression analysis:
1.Human PLAU was exclusively detectable in homozygous B-hPLAU/hPLAUR mice but not in wild-type mice.
2.Human PLAUR were exclusively detectable in mono/macrophages, granulocytes, and dendritic cells of homozygous B-hPLAU/hPLAUR mice but not in wild-type mice.
In vivo efficacy study
B-hPLAUR MC38 cells were able to establish tumors in B-hPLAU/hPLAUR mice in vivo and can be used for efficacy studies of anti-human PLAUR antibodies.
