Basic Information

Strain Name
C57BL/6-Vegfatm1(VEGFA)/Bcgen
Common Name
B-hVEGFA mice
Background
C57BL/6
Catalog number
110822
Related Genes
VEGFA (MVCD1, VEGF, VPF)
NCBI Gene ID

Targeting strategy

Gene targeting strategy for B-hVEGFA mice.

The exons 1-8 of mouse Vegfa gene that encode the full-length protein were replaced by human VEGFA exons 1-8 in B-hVEGFA mice.

Protein expression analysis

Strain specific VEGFA expression analysis in homozygous B-hVEGFA mice by ELISA. Mouse lung homogenates was collected from wild-type mice (+/+) and B-hVEGFA mice (H/H), and analyzed by ELISA with species-specific VEGFA kit. Mouse VEGFA was detectable in wild-type mice. Human VEGFA was exclusively detectable in B-hVEGFA mice but not in wild-type mice.

Fundus photographs of B-hVEGFA mice

Fundus photographs of B-hVEGFA mice. Fundus images shows that the  fundus morphology of B-hVEGFA mice has no significant change compared with wild-type mice (male, n=3).

Angiogenesis analysis

We investigated by immunohistochemistry the expression of mCD31 in the heart, liver, lung, kidney and eye of C57BL/6 mice and B-hVEGFA mice (female, 8 week-old, n=3). The results showed that there was no significant difference in the proportion of mCD31+ between C57BL/6 mice and B-hVEGFA mice in heart, liver, lung, kidney, eye. It is suggested that VEGFA humanized has no effect on angiogenesis.

In vivo efficacy of anti-human VEGFA antibody

Antitumor activity of anti-human VEGFA antibody in B-hVEGFA mice. (A) Anti-human VEGFA antibody inhibited B-hVEGFA MC38 tumor growth in B-hVEGFA mice. Murine colon cancer B-hVEGFA MC38 cells were subcutaneously implanted into homozygous B-hVEGFA mice (female, 6-7-week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were treated with anti-human VEGFA antibody bevacizumab and schedules indicated in panel A. (B) Body weight changes during treatment. (C) Proportion of CD31+ cell area of total area analyzed in tumor tissue. As shown in panel A, anti-human VEGFA antibody were efficacious in controlling tumor growth in B-hVEGFA mice. As shown in panel C, anti-human VEGFA antibody bevacizumab inhibits vascular endothelial cell proliferation, demonstrating that the B-hVEGFA mice provide a powerful preclinical model for in vivo evaluation of anti-human VEGFA antibody. Values are expressed as mean ± SEM.

Summary

Protein expression analysis:

Human VEGFA was exclusively detectable in lung homogenates of B-hVEGFA mice but not in wild-type mice.

Fundus photographs of B-hVEGFA mice 

Fundus images show the  fundus morphology of B-hVEGFA mice showed no significant changes compared with wild-type mice.

Angiogenesis analysis

There was no significant difference in the proportion of mCD31+ between C57BL/6 mice and B-hVEGFA mice in heart, liver, lung, kidney, eye. It is suggested that VEGFA humanized has no effect on angiogenesis.

In vivo efficacy:

Anti-human VEGFA antibody was efficacious in controlling tumor growth and the proliferation of  vascular endothelial cell in B-hVEGFA mice.

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