| First Author | Apicella I | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 12 | Pages | 3635-3646 |
| PubMed ID | 29925004 | Mgi Jnum | J:271257 |
| Mgi Id | MGI:6278486 | Doi | 10.1016/j.celrep.2018.05.067 |
| Citation | Apicella I, et al. (2018) Full Functional Knockout of Placental Growth Factor by Knockin with an Inactive Variant Able to Heterodimerize with VEGF-A. Cell Rep 23(12):3635-3646 |
| abstractText | Placental growth factor (PlGF) is a proangiogenic member of the vascular endothelial growth factor (VEGF) family playing a central role in pathological angiogenesis. PlGF-DE is a PlGF variant unable to bind vascular endothelial growth factor receptor 1 (VEGFR-1) but still able to generate heterodimer with VEGF-A. We have generated PlGF-DE knockin mice that are vital and fertile and show unaltered expression of Plgf, Vegf-a, Vegfr-1, and Vegfr-2 compared with wild-type mice. Interestingly, these mutants showed additional and remarkable angiogenesis impairment in tumor growth, hindlimb ischemia, and choroidal neovascularization compared with both PlGF knockout and wild-type mice. These findings provided insights on VEGF-A/PlGF heterodimer function, which was able to rescue neovascularization and vascular leakage in PlGF-DE knockin mice. Collectively, these data show that PlGF-DE knockin mouse could be considered the full functional knockout of PlGF, suggesting a reassessment of the phenotypes of knockout mice for the genes whose products are able to generate heterodimeric proteins. |
