Basic Information
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Targeting strategy
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Gene targeting strategy for B-hCCN2 mice.The exons 1-5 of mouse Ccn2 gene were replaced by human CCN2 exons 1-5 in B-hCCN2 mice.
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mRNA expression analysis
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Strain specific analysis of CCN2 gene expression in wild-type mice and B-hCCN2 mice by RT-PCR. Mouse Ccn2 mRNA was detectable in kidney of wild-type mice (+/+). Human CCN2 mRNA was detectable only in homozygous B-hCCN1 mice but not in wild-type mice.
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Protein expression analysis
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Strain specific CCN2 expression analysis in homozygous B-hCCN2 mice by Western blot. Kidney tissue was collected from wild-type C57BL/6 mice (+/+) and homozygous B-hCCN2 mice (H/H), and analyzed by western blot with anti-CCN2 antibody. CCN2 was detectable in wild type mice and homozygous B-hCCN2 mice, as the antibody is crossly reactive with CCN2 in human and mice.
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In vivo efficacy of anti-human CCN2 antibody with bleomycin-induced B-hCCN2 mice
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Anti-human CCN2 antibody inhibits collagen deposition in lungs of bleomycin-treated B-hCCN2 mice. B-hCCN2 mice were assigned to one saline non-bleomycin control group (n=4) and two bleomycin-treated fibrosis groups (n=9) which were treated with pamrevlumab (in house, anti-human CCN2) or vehicle. Pamrevlumab treatment was able to improve bleomycin-induced weight loss in B-hCCN2 mice(A). Fibrosis in this model was scored by the standard measure of total lung HYP. In control mice, bleomycin treatment increases HYP content compared with controls. Compared with vehicle-treated bleomycin controls, pamrevlumab treatment resulted in a reduction in mean induced lung HYP content (B). Values are expressed as mean ± SEM. *** p<0.001, **p<0.01.
