{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:29:50Z","timestamp":1787164190133,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["Translink 603049"],"award-info":[{"award-number":["Translink 603049"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Two well\u2010characterized carbohydrate epitopes are absent in humans but present in other mammals. These are galactose\u2010\u03b11,3\u2010galactose (\u03b1Gal) and\n                    <jats:italic>N<\/jats:italic>\n                    \u2010glycolylneuraminic acid (Neu5Gc) which are introduced by the activities of two enzymes including \u03b1(1,3) galactosyltransferase (encoded by the\n                    <jats:italic>GGTA1<\/jats:italic>\n                    gene) and CMP\u2010Neu5Gc hydroxylase (encoded by the\n                    <jats:italic>CMAH<\/jats:italic>\n                    gene) that are inactive in humans but present in cattle. Hence, bovine\u2010derived products are antigenic in humans who receive bioprosthetic heart valves (BHVs) or those that suffer from red meat syndrome. Using programmable nucleases, we disrupted (knockout, KO)\n                    <jats:italic>GGTA1<\/jats:italic>\n                    and\n                    <jats:italic>CMAH<\/jats:italic>\n                    genes encoding for the enzymes that catalyse the synthesis of \u03b1Gal and Neu5Gc, respectively, in both male and female bovine fibroblasts. The KO in clonally selected fibroblasts was detected by polymerase chain reaction (PCR) and confirmed by Sanger sequencing. Selected fibroblasts colonies were used for somatic cell nuclear transfer (SCNT) to produce cloned embryos that were implanted in surrogate recipient heifers. Fifty\u2010three embryos were implanted in 33 recipients heifers; 3 pregnancies were carried to term and delivered 3 live calves. Primary cell cultures were established from the 3 calves and following molecular analyses confirmed the genetic deletions. FACS analysis showed the double\u2010KO phenotype for both antigens confirming the mutated genotypes. Availability of such cattle double\u2010KO model lacking both \u03b1Gal and Neu5Gc offers a unique opportunity to study the functionality of BHV manufactured with tissues of potentially lower immunogenicity, as well as a possible new clinical approaches to help patients with red meat allergy syndrome due to the presence of\u00a0these xenoantigens in the diet.\n                  <\/jats:p>","DOI":"10.1111\/xen.12524","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T05:32:12Z","timestamp":1558503132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Generation of cattle knockout for galactose\u2010\u03b11,3\u2010galactose and N\u2010glycolylneuraminic acid antigens"],"prefix":"10.1111","volume":"26","author":[{"given":"Andrea","family":"Perota","sequence":"first","affiliation":[{"name":"Avantea Laboratory of Reproductive Technologies Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Lagutina","sequence":"additional","affiliation":[{"name":"Avantea Laboratory of Reproductive Technologies Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Duchi","sequence":"additional","affiliation":[{"name":"Avantea Laboratory of Reproductive Technologies Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Zanfrini","sequence":"additional","affiliation":[{"name":"Avantea Laboratory of Reproductive Technologies Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Lazzari","sequence":"additional","affiliation":[{"name":"Avantea Laboratory of Reproductive Technologies Cremona Italy"},{"name":"Fondazione Avantea Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul","family":"Judor","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie UMR 1064 INSERM, Universit\u00e9 de Nantes Nantes France"},{"name":"Institut de Transplantation Urologie N\u00e9phrologie (ITUN) CHU Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Conchon","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie UMR 1064 INSERM, Universit\u00e9 de Nantes Nantes France"},{"name":"Institut de Transplantation Urologie N\u00e9phrologie (ITUN) CHU Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Marie","family":"Bach","sequence":"additional","affiliation":[{"name":"IECM, Immuno\u2010endocrinology, EA4644 Oniris University of Nantes, USC1383 INRA, Oniris Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomaso","family":"Bottio","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Unit \u2010 Department of Cardiac Thoracic and Vascular Sciences and Public Health \u2010 Padova University School of Medicine and CORIS Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gino","family":"Gerosa","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Unit \u2010 Department of Cardiac Thoracic and Vascular Sciences and Public Health \u2010 Padova University School of Medicine and CORIS Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Costa","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Transplantation Division, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) Hospitalet de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Gali\u00f1anes","sequence":"additional","affiliation":[{"name":"Reparative Therapy of the Heart, Vall d\u2019Hebron Research Institute (VHIR) and Department of Cardiac Surgery University Hospital Vall d\u2019Hebron, Autonomous University of Barcelona (AUB) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Christian","family":"Roussel","sequence":"additional","affiliation":[{"name":"Department of Thoracic and CardioVascular Surgery Nantes Hospital University Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4761-3571","authenticated-orcid":false,"given":"Vered","family":"Padler\u2010Karavani","sequence":"additional","affiliation":[{"name":"The George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Cozzi","sequence":"additional","affiliation":[{"name":"Transplant Immunology Unit Padua General Hospital Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul","family":"Soulillou","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Transplantation et Immunologie UMR 1064 INSERM, Universit\u00e9 de Nantes Nantes France"},{"name":"Institut de Transplantation Urologie N\u00e9phrologie (ITUN) CHU Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9529-6136","authenticated-orcid":false,"given":"Cesare","family":"Galli","sequence":"additional","affiliation":[{"name":"Avantea Laboratory of Reproductive Technologies Cremona Italy"},{"name":"Fondazione Avantea Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4771-6_10"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01053190"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301195"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2002.02138.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12142"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12019"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1330"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12044"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12260"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12354"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(19991215)47:4<439::AID-JBM1>3.0.CO;2-O"},{"issue":"1","key":"e_1_2_8_13_1","first-page":"124","article-title":"Anti alpha\u2010gal immune response following porcine bioprosthesis implantation in children","volume":"19","author":"Park CS","year":"2010","journal-title":"J Heart Valve Dis"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12406"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2011.0046"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2010.08.064"},{"issue":"3","key":"e_1_2_8_17_1","first-page":"383","article-title":"Gal\u2010knockout bioprostheses exhibit less immune stimulation compared to standard biological heart valves","volume":"22","author":"McGregor CG","year":"2013","journal-title":"J Heart Valve Dis"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.03.055"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.12.1947"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40629-016-0098-0"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2016.07.002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417508112"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11462-z"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171477"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078119"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9872.1000333"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.5661\/bger-28-147"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310478110"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000190422.66657.f1"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12089"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.171322.113"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2015.04.024"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20890"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1106422108"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresprot.2005.10.004"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/15362300260339476"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0300493"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12131"}],"container-title":["Xenotransplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fxen.12524","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/xen.12524","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/xen.12524","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/xen.12524","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T15:27:11Z","timestamp":1694273231000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/xen.12524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,22]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1111\/xen.12524"],"URL":"https:\/\/doi.org\/10.1111\/xen.12524","archive":["Portico"],"relation":{},"ISSN":["0908-665X","1399-3089"],"issn-type":[{"value":"0908-665X","type":"print"},{"value":"1399-3089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,22]]},"assertion":[{"value":"2019-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12524"}}