A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10
| Autor: | Haitian Zhao, Pallavi Chandakkar, Prodyot K. Chatterjee, Lionel Blanc, Philippe Marambaud, Fabien Campagne, Santiago Ruiz, Christine N. Metz, Julien Papoin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Endothelium Angiogenesis Article Neovascularization Angiopoietin-2 03 medical and health sciences 0302 clinical medicine Immunity Blocking antibody medicine Growth Differentiation Factor 2 Animals Lactation Antibodies Blocking Retina Multidisciplinary biology Neovascularization Pathologic business.industry Retinal Vessels Endoglin Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Animals Newborn Bone Morphogenetic Proteins biology.protein Female Telangiectasia Hereditary Hemorrhagic Endothelium Vascular Antibody medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4 and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation. Here, we investigated whether the transmammary delivery route could improve the ease and consistency of administering anti-BMP9/10 antibodies in the postnatal retinal angiogenesis model. We found that anti-BMP9/10 antibodies, when intraperitoneally injected into lactating dams, are efficiently transferred into the blood circulation of lactationally-exposed neonatal pups. Strikingly, pups receiving anti-BMP9/10 antibodies via lactation displayed consistent and robust vascular pathology in the retina, which included hypervascularization and defects in arteriovenous specification, as well as the presence of multiple and massive arteriovenous malformations. Furthermore, RNA-Seq analyses of neonatal retinas identified an increase in the key pro-angiogenic factor, angiopoietin-2, as the most significant change in gene expression triggered by the transmammary delivery of anti-BMP9/10 antibodies. Transmammary-delivered BMP9/10 immunoblocking in the mouse neonatal retina is therefore a practical, noninvasive, reliable and robust model of HHT vascular pathology. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|