2026-06-29T02:37:34Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1339372026-04-23T10:24:27Zcom_20.500.14352_14col_20.500.14352_15

Effect of a truncated mutant factor V on hemostatic function and embryonic development in mice Miguel Batuecas, Andrea De Pablo Moreno, Juan Andrés Porras, Néstor Bermejo Álvarez, Pablo González-Brusi, Leopoldo Serrano, Luis J. De Pablo-Moreno, Javier M. Sánchez, María José García-Arranz, Mariano Rodríguez Bertos, Antonio Manuel Chumappumkal, Bilgimol Joseph Revuelta Rueda, Luis Liras Martín, Antonio This research was funded by the Association for Research and Cure of Factor V deficiency (ASDEFAV), grant number ASDEFAV/2021–25; the Complutense University of Madrid and Banco Santander, grant number CT63/19-CT64/19; the Spanish Ministry of Science and Innovation, grant number PID2020-117501RB-I00; the Community of Madrid, grant number CT85/23; MJS work was supported by a Spanish María de Maeztu Unit excellence grant CEX-2020-001088-M to the CABD, and by Regional Government of Andalusia, Department of Innovation (PAI-BIO-295). Factor V is an essential protein in the blood clotting process and plays a central role in secondary hemostasis. Its deficiency causes a rare inherited disorder characterized by episodes of severe bleeding, some of which can be life-threatening. Although previous studies have established that factor V is essential for normal embryonic development, its specific contribution to vascular maturation remains incompletely understood, factor V is believed to contribute to blood vessel stabilization and regulate angiogenesis through its interaction with thrombin. In a recent study, a CRISPR-engineered mouse model intended to produced a mild factor V deficiency disease, unexpectedly produced a frameshift mutation in the A3 domain, resulting in a truncated protein. Factor V levels in healthy embryonic mouse tissues were assessed to investigate its role at different developmental stages. The mutation markedly impaired viability, as homozygous mice exhibited a lethal phenotype with severe bleeding and perinatal death, along with impaired coagulation function. Histopathological and immunohistochemical analyses indicated a link between factor V deficiency, thrombin and α-smooth muscle actin, potentially affecting proangiogenic signaling and embryonic vascular formation. Factor V gene expression increased during late embryogenesis, underscoring its importance in vascular development and maturation. Overall, these findings are consistent with a role for factor V in stabilizing embryonic blood vessels and modulating thrombin-dependent angiogenesis, and add further detail on the developmental impact of its deficiency and the pathogenesis of congenital bleeding disorders. 2026-03-11T11:52:18Z 2026-03-11T11:52:18Z 2026 journal article Miguel-Batuecas, A., De Pablo-Moreno, J. A., Porras, N., Bermejo-Álvarez, P., González-Brusi, L., Serrano, L. J., De Pablo-Moreno, J. M., Sánchez, M. J., García-Arranz, M., Rodríguez-Bertos, A., Chumappumkal Joseph, B., Revuelta, L., & Liras, A. (2026). Effect of a truncated mutant factor V on hemostatic function and embryonic development in mice. Scientific reports, 16(1), 8460. https://doi.org/10.1038/s41598-026-38387-w 10.1038/s41598-026-38387-w https://hdl.handle.net/20.500.14352/133937 2045-2322 https://doi.org/10.1038/s41598-026-38387-w 41680367 https://pubmed.ncbi.nlm.nih.gov/41680367/ eng info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-117501RB-I00/ES/ESTUDIO DE ALTERACIONES EN EMBRIOGENESIS Y FECUNDACION QUE AFECTAN A LA EFICACIA REPRODUCTIVA DE ANIMALES DE GRANJA / http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internationa Nature Research