{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T20:25:11Z","timestamp":1792959911464,"version":"4.5.0"},"reference-count":25,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5073","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1992,8,21]]},"abstract":"<jats:p>Cystic fibrosis results from defects in the gene encoding a cyclic adenosine monophosphate-dependent chloride ion channel known as the cystic fibrosis transmembrane conductance regulator (CFTR). To create an animal model for cystic fibrosis, mice were generated from embryonic stem cells in which the CFTR gene was disrupted by gene targeting. Mice homozygous for the disrupted gene display many features common to young human cystic fibrosis patients, including failure to thrive, meconium ileus, alteration of mucous and serous glands, and obstruction of glandlike structures with inspissated eosinophilic material. Death resulting from intestinal obstruction usually occurs before 40 days of age.<\/jats:p>","DOI":"10.1126\/science.257.5073.1083","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T23:03:06Z","timestamp":1160089386000},"page":"1083-1088","source":"Crossref","is-referenced-by-count":759,"title":["An Animal Model for Cystic Fibrosis Made by Gene Targeting"],"prefix":"10.1126","volume":"257","author":[{"given":"John N.","family":"Snouwaert","sequence":"first","affiliation":[{"name":"Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7020"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen K.","family":"Brigman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7020"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Latour","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7020"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia N.","family":"Malouf","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Boucher","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7020"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Smithies","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly H.","family":"Koller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7020"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1001\/archpedi.1938.01980140114013","volume":"56","year":"1938","unstructured":"ANDERSEN, D.H., Cystic fibrosis of the pancreas and its relation to celiac disease - A clinical and pathologic study, AMERICAN JOURNAL OF DISEASES OF CHILDREN 56: 344 (1938).","journal-title":"AMERICAN JOURNAL OF DISEASES OF CHILDREN"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/352070a0","volume":"352","year":"1991","unstructured":"BARASCH, J, DEFECTIVE ACIDIFICATION OF INTRACELLULAR ORGANELLES IN CYSTIC-FIBROSIS, NATURE 352: 70 (1991).","journal-title":"NATURE"},{"key":"e_1_2_1_3_1","unstructured":"Boat T. F. The Metabolic Basis of Inherited Disease 6 2649 (1989)."},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1373908"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1126\/science.256.5058.774","volume":"256","year":"1992","unstructured":"COLLINS, F.S., CYSTIC-FIBROSIS - MOLECULAR-BIOLOGY AND THERAPEUTIC IMPLICATIONS, SCIENCE 256: 774 (1992).","journal-title":"SCIENCE"},{"key":"e_1_2_1_6_1","first-page":"212","year":"1984","unstructured":"diSant'Agnese, P. A., Cystic Fibrosis: 212 (1984).","journal-title":"Cystic Fibrosis"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1542\/peds.37.5.833","volume":"37","year":"1966","unstructured":"DONNISON, A.B., A REVIEW OF 164 CHILDREN WITH MECONIUM ILEUS SEEN AT CHILDRENS HOSPITAL MEDICAL CENTER BOSTON, PEDIATRICS 37: 833 (1966).","journal-title":"PEDIATRICS"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/BF02513027","volume":"1","year":"1992","unstructured":"DORIN, J.R., TRANSGENIC RES 1: 101 (1992).","journal-title":"TRANSGENIC RES"},{"key":"e_1_2_1_9_1","first-page":"238","volume":"37","year":"1944","unstructured":"FARBER, S, ARCHIVES OF PATHOLOGY 37: 238 (1944).","journal-title":"ARCHIVES OF PATHOLOGY"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1542\/peds.54.3.293","volume":"54","year":"1974","unstructured":"FOX, W.W., PEDIATRICS 54: 293 (1974).","journal-title":"PEDIATRICS"},{"key":"e_1_2_1_11_1","first-page":"4.7.1","year":"1989","unstructured":"Gilman, M., Current Protocols in Molecular Biology: 4.7.1 (1989).","journal-title":"Current Protocols in Molecular Biology"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/326292a0","volume":"326","year":"1987","unstructured":"HOOPER, M, HPRT-DEFICIENT (LESCH-NYHAN) MOUSE EMBRYOS DERIVED FROM GERMLINE COLONIZATION BY CULTURED-CELLS, NATURE 326: 292 (1987).","journal-title":"NATURE"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2570460"},{"key":"e_1_2_1_14_1","unstructured":"KNOWLES M.R. COMMUNICATION."},{"key":"e_1_2_1_15_1","first-page":"10730","volume":"88","year":"1991","unstructured":"KOLLER, B.H., TOWARD AN ANIMAL-MODEL OF CYSTIC-FIBROSIS - TARGETED INTERRUPTION OF EXON-10 OF THE CYSTIC-FIBROSIS TRANSMEMBRANE REGULATOR GENE IN EMBRYONIC STEM-CELLS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 10730 (1991).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1172\/JCI115358","volume":"88","year":"1991","unstructured":"MARINO, C.R., LOCALIZATION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR IN PANCREAS, JOURNAL OF CLINICAL INVESTIGATION 88: 712 (1991).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0016-5085(84)80029-3","volume":"86","year":"1984","unstructured":"MCCARTHY, V.P., APPENDICEAL ABSCESS IN CYSTIC-FIBROSIS - A DIAGNOSTIC CHALLENGE, GASTROENTEROLOGY 86: 564 (1984).","journal-title":"GASTROENTEROLOGY"},{"key":"e_1_2_1_18_1","first-page":"149","volume":"96","year":"1973","unstructured":"OPPENHEIMER, E.H., CYSTIC-FIBROSIS OF PANCREAS, ARCHIVES OF PATHOLOGY 96: 149 (1973).","journal-title":"ARCHIVES OF PATHOLOGY"},{"key":"e_1_2_1_19_1","first-page":"241","volume":"2","year":"1975","unstructured":"Oppenheimer, E. H., Perspectives in Pediatric Pathology 2: 241 (1975).","journal-title":"Perspectives in Pediatric Pathology"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2475911"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2772657"},{"key":"e_1_2_1_22_1","first-page":"303","volume":"106","year":"1982","unstructured":"STURGESS, J, QUANTITATIVE-EVALUATION OF THE DEVELOPMENT OF TRACHEAL SUB-MUCOSAL GLANDS IN INFANTS WITH CYSTIC-FIBROSIS AND CONTROL INFANTS, AMERICAN JOURNAL OF PATHOLOGY 106: 303 (1982).","journal-title":"AMERICAN JOURNAL OF PATHOLOGY"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0888-7543(91)90312-3","volume":"10","year":"1991","unstructured":"TATA, F, CLONING THE MOUSE HOMOLOG OF THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE, GENOMICS 10: 301 (1991).","journal-title":"GENOMICS"},{"key":"e_1_2_1_24_1","first-page":"115","year":"1984","unstructured":"Taussig, L. M., Cystic Fibrosis: 115 (1984).","journal-title":"Cystic Fibrosis"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/353434a0","volume":"353","year":"1991","unstructured":"TREZISE, AEO, INVIVO CELL-SPECIFIC EXPRESSION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR, NATURE 353: 434 (1991).","journal-title":"NATURE"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.257.5073.1083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T23:57:05Z","timestamp":1705103825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.257.5073.1083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,8,21]]},"references-count":25,"journal-issue":{"issue":"5073","published-print":{"date-parts":[[1992,8,21]]}},"alternative-id":["10.1126\/science.257.5073.1083"],"URL":"https:\/\/doi.org\/10.1126\/science.257.5073.1083","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,8,21]]}}}