{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:16:28Z","timestamp":1790856988744,"version":"4.1.0"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5612","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,3,7]]},"abstract":"<jats:p>\n            Mutations in the cytochrome P450 family 1, subfamily B, polypeptide 1 (\n            <jats:italic>CYP1B1<\/jats:italic>\n            ) gene are a common cause of human primary congenital glaucoma (PCG). Here we show that\n            <jats:italic>Cyp1b1<\/jats:italic>\n            <jats:sup>\u2013\/\u2013<\/jats:sup>\n            mice have ocular drainage structure abnormalities resembling those reported in human PCG patients. Using\n            <jats:italic>Cyp1b1<\/jats:italic>\n            <jats:sup>\u2013\/\u2013<\/jats:sup>\n            mice, we identified the tyrosinase gene (\n            <jats:italic>Tyr<\/jats:italic>\n            ) as a modifier of the drainage structure phenotype, with\n            <jats:italic>Tyr<\/jats:italic>\n            deficiency increasing the magnitude of dysgenesis. The severe dysgenesis in eyes lacking both CYP1B1 and TYR was alleviated by administration of the tyrosinase product dihydroxyphenylalanine (\n            <jats:sc>l<\/jats:sc>\n            -dopa).\n            <jats:italic>Tyr<\/jats:italic>\n            also modified the drainage structure dysgenesis in mice with a mutant\n            <jats:italic>Foxc1<\/jats:italic>\n            gene, which is also involved in PCG. These experiments raise the possibility that a tyrosinase\/\n            <jats:sc>l<\/jats:sc>\n            -dopa pathway modifies human PCG, which could open new therapeutic avenues.\n          <\/jats:p>","DOI":"10.1126\/science.1080095","type":"journal-article","created":{"date-parts":[[2003,3,6]],"date-time":"2003-03-06T22:06:37Z","timestamp":1046988397000},"page":"1578-1581","source":"Crossref","is-referenced-by-count":182,"title":["Modification of Ocular Defects in Mouse Developmental Glaucoma Models by Tyrosinase"],"prefix":"10.1126","volume":"299","author":[{"given":"Richard T.","family":"Libby","sequence":"first","affiliation":[{"name":"The Jackson Laboratory,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Smith","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory,"},{"name":"The Howard Hughes Medical Institute, Bar Harbor, ME 04609, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Savinova","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Bar Harbor, ME 04609, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Zabaleta","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Bar Harbor, ME 04609, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice E.","family":"Martin","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory,"},{"name":"The Howard Hughes Medical Institute, Bar Harbor, ME 04609, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon W. M.","family":"John","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory,"},{"name":"The Howard Hughes Medical Institute, Bar Harbor, ME 04609, USA."},{"name":"Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","unstructured":"R. Ritch M. B. Shields T. Krupin in The Glaucomas Clinical Science R. Ritch M. B. Shields T. Krupin Eds. (Mosby St. Louis MO ed. 2 1996) vol. 2."},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/338709"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.10.1185"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2000.126"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/493"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1980.tb00142.x"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.3.367"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-1-3"},{"key":"e_1_3_1_9_3","unstructured":"; available at www.biomedcentral.com\/1471-213X\/1\/3."},{"key":"e_1_3_1_10_2","unstructured":"O. V. Savinova R. S. Smith S. W. M. John unpublished data."},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1955.00930010791002"},{"key":"e_1_3_1_12_2","first-page":"507","volume":"56","author":"Maumenee E. A.","year":"1958","unstructured":"Maumenee E. A., Trans. Am. Ophthalmol. Soc. 56, 507 (1958).","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"e_1_3_1_13_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.4.625"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.7.1021"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990315)405:3<394::AID-CNE9>3.0.CO;2-Y"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/374643a0"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/374640a0"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19981221)402:3<402::AID-CNE8>3.0.CO;2-0"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-17-06501.2000"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0741829.x"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00257.x"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1996.0118"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/73902"},{"key":"e_1_3_1_25_2","first-page":"315","volume":"28","author":"Chen H.","year":"2000","unstructured":"Chen H., Howald W. N., Juchau M. R., Drug Metab. Dispos. 28, 315 (2000).","journal-title":"Drug Metab. Dispos."},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1996.0079"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.3109\/13816818809031473"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1984.tb01085.x"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1997.tb00461.x"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.48.31801"},{"key":"e_1_3_1_31_2","unstructured":"We thank F. Farley and J. Smith for assistance in preparing the manuscript and M. Anderson D. Gould T. Gridley and T. O'Brien for critical reading of the manuscript and L. Bechtold for assistance with electron microscopy. Scientific support services at The Jackson Laboratory are subsidized by a core grant from the National Cancer Institute (grant CA34196). S.W.M.J. is an Associate Investigator of The Howard Hughes Medical Institute."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1080095","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T02:07:35Z","timestamp":1704852455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1080095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,7]]},"references-count":31,"journal-issue":{"issue":"5612","published-print":{"date-parts":[[2003,3,7]]}},"alternative-id":["10.1126\/science.1080095"],"URL":"https:\/\/doi.org\/10.1126\/science.1080095","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,7]]}}}