{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:37:24Z","timestamp":1770903444526,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,11,17]],"date-time":"2011-11-17T00:00:00Z","timestamp":1321488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/us\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>\n                    Crigler\u2010Najjar type I (CNI) syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused by uridine diphosphoglucuronosyltransferase 1A1 (UGT1A1) deficiency. The disease is lethal due to bilirubin\u2010induced neurological damage unless phototherapy is applied from birth. However, treatment becomes less effective during growth, and liver transplantation is required. To investigate the pathophysiology of the disease and therapeutic approaches in mice, we generated a mouse model by introducing a premature stop codon in the UGT1a1 gene, which results in an inactive enzyme. Homozygous mutant mice developed severe jaundice soon after birth and died within 11d, showing significant cerebellar alterations. To rescue neonatal lethality, newborns were injected with a single dose of adeno\u2010associated viral vector 9 (AAV9) expressing the human UGT1A1. Gene therapy treatment completely rescued all AAV\u2010treated mutant mice, accompanied by lower plasma bilirubin levels and normal brain histology and motor coordination. Our mouse model of CNI reproduces genetic and phenotypic features of the human disease. We have shown, for the first time, the full recovery of the lethal effects of neonatal hyperbilirubinemia. We believe that, besides gene\u2010addition\u2010based therapies, our mice could represent a very useful model to develop and test novel technologies based on gene correction by homologous recombination.\u2014Bortolussi, G., Zentilin, L., Baj, G., Giraudi, P., Bellarosa, C., Giacca, M., Tiribelli, C., Muro, A. F. Rescue of bilirubin\u2010induced neonatal lethality in a mouse model of Crigler\u2010Najjar syndrome type I by AAV9\u2010mediated gene transfer.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 1052\u20101063 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-195461","type":"journal-article","created":{"date-parts":[[2011,11,18]],"date-time":"2011-11-18T02:24:27Z","timestamp":1321583067000},"page":"1052-1063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Rescue of bilirubin\u2010induced neonatal lethality in a mouse model of Crigler\u2010Najjar syndrome type I by AAV9\u2010mediated gene transfer"],"prefix":"10.1096","volume":"26","author":[{"given":"Giulia","family":"Bortolussi","sequence":"first","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Zentilin","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Baj","sequence":"additional","affiliation":[{"name":"Basic Research and Integrative Neuroscience (BRAIN) Centre for Neuroscience Department of Life Sciences University of Trieste Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Giraudi","sequence":"additional","affiliation":[{"name":"Centro Studi Fegato, Fondazione Italiana Fegato AREA Science Park, Campus Basovizza Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Bellarosa","sequence":"additional","affiliation":[{"name":"Centro Studi Fegato, Fondazione Italiana Fegato AREA Science Park, Campus Basovizza Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Giacca","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Tiribelli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Trieste Trieste Italy"},{"name":"Centro Studi Fegato, Fondazione Italiana Fegato AREA Science Park, Campus Basovizza Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s F.","family":"Muro","sequence":"additional","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,11,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(98)00044-1"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z"},{"key":"e_1_2_6_4_1","first-page":"169","article-title":"Congenital familial nonhemolytic jaundice with kernicterus","volume":"10","author":"Crigler J. 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