Basic Information
-
Gene targeting strategy
-
Gene targeting strategy for B-hCCN2 mice. Exons 1-5 of mouse Ccn2 gene were replaced by human CCN2 exons 1-5 in B-hCCN2 mice.
-
mRNA expression analysis
-
Species-specific CCN2 gene expression analysis in wild-type and B-hCCN2 mice by RT-PCR. Murine Ccn2 mRNA was detected in kidney cells isolated from wild-type (+/+) mice, while human CCN2 mRNA was exclusively detected in homozygous B-hCCN2 (H/H) mice.
-
Protein expression analysis
-
Species-specific CCN2 protein expression analysis in B-hCCN2 mice by Western blot. Kidney tissue was isolated from wild-type C57BL/6 (+/+) and homozygous B-hCCN2 (H/H) mice, and analyzed by western blot using a cross-reactive anti-m/hCCN2 antibody. Mouse and human CCN2 protein was detected in wild-type and homozygous B-hCCN2 mice.
-
In vivo efficacy of an anti-human CCN2 Ab in bleomycin-treated B-hCCN2 mice
-
Anti-human CCN2 antibody inhibits collagen deposition in the lungs of bleomycin-treated B-hCCN2 mice. Humanized B-hCCN2 mice were assigned to either a control (saline, non-bleomycin, n=4) group, or bleomycin-induced fibrosis (+/- pamrevlumab, n=9) groups. (A) Pamrevlumab (in house, anti-human CCN2 Ab) treatment improved bleomycin-induced weight loss in B-hCCN2 mice. (B) Fibrosis was scored by the standard measure of total lung hypertensive myocardial HYP. Bleomycin-vehicle treated mice increased HYP, while bleomycin-pamrevlumab treated mice showed a reduction in lung HYP content. Values are expressed as mean ± SEM. *** p<0.001, **p<0.01.
