B-hGDF15 mice

Basic Information

Gene targeting strategy

Gene targeting strategy for B-hGDF15 mice. The exons 1-2 of mouse Gdf15 gene that encode the full-length protein were replaced by human GDF15 exons 1-2 in B-hGDF15 mice.

mRNA expression analysis

Species-specific GDF15 gene expression analysis in wild-type and humanized B-hGDF15 mice by RT-PCR. Murine Gdf15 mRNA was detected in kidney tissue isolated from wild-type (+/+) mice, while human GDF15 mRNA was detected in B-hGDF15 mice.

Protein expression analysis

Strain-specific GDF15 expression analysis in wild-type C57BL/6 mice and homozygous B-hGDF15 mice by ELISA. Serum was collected from wild-type C57BL/6 mice (+/+) and homozygous B-hGDF15 mice (H/H), and analyzed by ELISA with species-specific GDF15 ELISA kit (R&D, Mouse/Rat GDF-15 Quantikine ELISA Kit: MGD150, Human GDF-15 Quantikine ELISA Kit: DGD150). Mouse GDF15 was exclusively detectable in wild-type mice and human GDF15 was exclusively detectable in homozygous B-hGDF15 mice. Values are expressed as mean ± SEM.

Tumor growth curve & body weight changes

Subcutaneous tumor growth of B-hGDF15 MC38 cells. B-hGDF15 MC38 cells (5×10⁵) and wild-type MC38 cells (5×10⁵) were subcutaneously implanted into homozygous B-hGDF15 mice (female, 6-8 weeks old, n=6). Tumor volume and body weight were measured twice a week. (A) Average tumor volume. (B) Body weight. The B-hGDF15 MC38 cell inoculation group shows a decreasing trend in body weight compared to the wild-type MC38 cell inoculation group. Volume was expressed in mm³ using the formula: V=0.5 X long diameter X short diameter². Results indicate that B-hGDF15 MC38 cells were able to establish tumors in vivo and can be used for efficacy studies. Values are expressed as mean ± SEM. Note: The B-hGDF15 MC38 tumor was only implanted in B-hGDF15 mice and has not been implanted in C57BL/6 mice.

In vivo efficacy of anti-human GDF15 antibodies

Antitumor activity of anti-human GDF15 antibody (ponsegromab analog, in-house) in B-hGDF15 mice. (A) B-hGDF15 MC38 tumor growth in B-hGDF15 mice. Murine colon cancer B-hGDF15 MC38 cells (5×10⁵) were subcutaneously implanted into homozygous B-hGDF15 mice (female, 9 weeks old, n=6). Mice were grouped when tumor volume reached approximately 100-150 mm³, at which time they were intraperitoneally injected with anti-human GDF15 antibody indicated in panel. (B) Body weight changes during treatment. (C) The weight change of each mouse in the group compared to Day 0. As shown in panel B and C, anti-human GDF15 antibody was effective in controlling the weight loss induced by B-hGDF15 MC38 in B-hGDF15 mice, demonstrating that the B-hGDF15 mice and B-hGDF15 MC38 provide a powerful preclinical model for in vivo evaluation of anti-human GDF15 antibodies. Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001. The overage of this tumor model is 50%.

Summary

mRNA expression：

Mouse Gdf15 mRNA was detectable in kidney of wild-type (+/+). Human GDF15 mRNA was detectable only in H/H but not in +/+ mice. 

Protein  expression：

Mouse GDF15 was exclusively detectable in wild-type mice and human GDF15 was exclusively detectable in homozygous B-hGDF15 mice.