2026-05-27T22:08:38Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/97982024-12-18T01:05:31Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169

Salter, Donald M. c67bdd4d-886f-4d06-9a04-795cad4a3471 600 Griffin, Meredyth b90b6796-95e3-4842-be23-173f730eefe3 600 Muir, Morwenna 8b73d7aa-c957-4611-93d4-d0a6a381ab02 600 Teo, Katy c3af4e22-fead-434b-b25e-7ebf3fcff045 600 Culley, Jayne cc3ee3ae-500b-4322-99ee-b549ac7306e4 600 Smith, James R. 41c1a3d6-7319-47af-87a0-67386bf78711 600 Gómez Cuadrado, Laura 9514b3a3-cf2c-47f7-8cbe-5a961c5653b5 600 Matchett, Kylie 52a60f1c-abb1-49ac-8d51-bd62a3b38248 600 Sims, Andrew H. 400aa54f-9705-4980-93bf-0822e64dfb9f 600 Hayward, Larry ab466874-e0c4-4179-9a76-7c8d87da7be6 600 Henderson, Neil C. 0ce0f856-89d9-4b36-80f1-6772028c8294 600 Brunton, Valerie G. 647cce9b-b9ca-4776-9053-5bfb5be6858d 600 2024-12-17T12:47:28Z 2024-12-17T12:47:28Z 2019-06 1754-8403 http://hdl.handle.net/10259/9798 10.1242/dmm.038612 1754-8411 Angiosarcomas are a rare group of tumours which have poor prognosis and limited treatment options. The development of new therapies has been hampered by a lack of good preclinical models. Here, we describe the development of an autochthonous mouse model of angiosarcoma driven by loss of p53 in VE-cadherin-expressing endothelial cells. Using Cdh5-Cre to drive recombination in adult endothelial cells, mice developed angiosarcomas with 100% penetrance upon homozygous deletion of Trp53 with a median lifespan of 325 days. In contrast, expression of the R172H mutant p53 resulted in formation of thymic lymphomas with a more rapid onset (median lifespan 151 days). We also used Pdgfrb-Cre-expressing mice, allowing us to target predominantly pericytes, as these have been reported as the cell of origin for a number of soft tissue sarcomas. Pdgfrb-Cre also results in low levels of recombination in venous blood endothelial cells in multiple tissues during development. Upon deletion of Trp53 in Pdgfrb-Cre-expressing mice (Pdgfrb-Cre, Trp53fl/fl mice), 65% developed lymphomas and 21% developed pleomorphic undifferentiated soft tissue sarcomas. None developed angiosarcomas. In contrast, 75% of Pdgfrb-Cre, Trp53R172H/R172H mice developed angiosarcomas, with 60% of these mice also developing lymphomas. The median lifespan of the Pdgfrb-Cre, Trp53R172H/R172H mice was 151 days. Re-implantation of angiosarcoma tumour fragments from Cdh5-Cre, Trp53fl/fl mice provided a more consistent and rapid model of angiosarcoma than the two spontaneous models. The ability to passage tumour fragments through the mouse provides a novel model which is amenable to preclinical studies and will help the development of potential new therapies for angiosarcoma. This work was supported by Cancer Research UK (C157/A15703, C157/A9148 and C6088/A12063), a Wellcome Trust Senior Research Fellowship in Clinical Science (103749) to N.C.H., a Wellcome Trust Clinical Training Fellowship to J.R.S., a Wellcome Trust Institutional Strategic Support Fund award, the Edinburgh and Lothians Health Foundation Margaret Lee Oncology fund, the Charon Fund (registered charity SC022161) and NHS Health Scotland. application/pdf eng The Company of Biologists Disease Models & Mechanisms. 2019, V. 12, n. 7 https://doi.org/10.1242/dmm.038612 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Angiosarcoma TRP53 Genetically engineered mouse model Lymphomas Tumour Oncología Salud Medicina Oncology Health Medicine Development of mouse models of angiosarcoma driven by p53 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Disease Models & Mechanisms 12 7 THUMBNAIL salter-dm&m_2019.pdf.jpg salter-dm&m_2019.pdf.jpg IM Thumbnail image/jpeg 5215 https://riubu.ubu.es/bitstream/10259/9798/4/salter-dm%26m_2019.pdf.jpg 1c8a0ea625f383130c42232794f4b329 MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 1362 https://riubu.ubu.es/bitstream/10259/9798/3/license.txt 5d013bfa6e473ff0db22cd82a4d71a70 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/9798/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL salter-dm&m_2019.pdf salter-dm&m_2019.pdf application/pdf 9478348 https://riubu.ubu.es/bitstream/10259/9798/1/salter-dm%26m_2019.pdf 2e27a355e47c40393e755930df032482 MD5 1 10259/9798 oai:riubu.ubu.es:10259/9798 2024-12-18 02:05:31.177 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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