{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:23:53Z","timestamp":1792027433155,"version":"4.4.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,10,9]]},"abstract":"<jats:p>\n                    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation in the kidney, liver, and pancreas and is associated often with cardiovascular abnormalities such as hypertension, mitral valve prolapse, and intracranial aneurysms. It is caused by mutations in\n                    <jats:italic>PKD1<\/jats:italic>\n                    or\n                    <jats:italic>PKD2<\/jats:italic>\n                    , encoding polycystin-1 and -2, which together form a cell surface nonselective cation ion channel.\n                    <jats:italic>Pkd2<\/jats:italic>\n                    \u2212\/\u2212 mice have cysts in the kidney and pancreas and defects in cardiac septation, whereas\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>del34<\/jats:sup>\n                    <\/jats:italic>\n                    \u2212\/\u2212 and\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>L<\/jats:sup>\n                    <\/jats:italic>\n                    \u2212\/\u2212 mice have cysts but no cardiac abnormalities, although vascular fragility was reported in the latter. Here we describe mice carrying a targeted mutation in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    (\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>del17\u201321\u03b2geo<\/jats:sup>\n                    <\/jats:italic>\n                    ), which defines its expression pattern by using a\n                    <jats:italic>lacZ<\/jats:italic>\n                    reporter gene and may identify novel functions for polycystin-1. Although\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>del17\u201321\u03b2geo<\/jats:sup>\n                    <\/jats:italic>\n                    +\/\u2212 adult mice develop renal and hepatic cysts,\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>del17\u201321\u03b2geo<\/jats:sup>\n                    <\/jats:italic>\n                    \u2212\/\u2212 embryos die at embryonic days 13.5\u201314.5 from a primary cardiovascular defect that includes double outflow right ventricle, disorganized myocardium, and abnormal atrio-ventricular septation. Skeletal development is also severely compromised. These abnormalities correlate with the major sites of\n                    <jats:italic>Pkd1<\/jats:italic>\n                    expression. During nephrogenesis,\n                    <jats:italic>Pkd1<\/jats:italic>\n                    is expressed in maturing tubular epithelial cells from embryonic day 15.5. This expression coincides with the onset of cyst formation in\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>del34<\/jats:sup>\n                    <\/jats:italic>\n                    \u2212\/\u2212,\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>L<\/jats:sup>\n                    <\/jats:italic>\n                    \u2212\/\u2212, and\n                    <jats:italic>Pkd2<\/jats:italic>\n                    \u2212\/\u2212 mice, supporting the hypothesis that polycystin-1 and polycystin-2 interact\n                    <jats:italic>in vivo<\/jats:italic>\n                    and that their failure to do so leads to abnormalities in tubule morphology and function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.211191098","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"12174-12179","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":271,"title":["Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the\n                    <i>Pkd1<\/i>\n                    gene"],"prefix":"10.1073","volume":"98","author":[{"given":"Catherine","family":"Boulter","sequence":"first","affiliation":[{"name":"Departments of Genetics, Biochemistry, and Medical Genetics, University of Cambridge, Cambridge CB2 1TN, United Kingdom; Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, London 5W17 ORE, United Kingdom; and Department of Molecular and Cellular Pathology, University of Dundee, Dundee DD195Y, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Mulroy","sequence":"additional","affiliation":[{"name":"Departments of Genetics, Biochemistry, and Medical Genetics, University of Cambridge, Cambridge CB2 1TN, United Kingdom; Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, London 5W17 ORE, United Kingdom; and Department of Molecular and Cellular Pathology, University of Dundee, Dundee DD195Y, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Webb","sequence":"additional","affiliation":[{"name":"Departments of Genetics, Biochemistry, and Medical Genetics, University of Cambridge, Cambridge CB2 1TN, United Kingdom; Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, London 5W17 ORE, United Kingdom; and Department of Molecular and Cellular Pathology, University of Dundee, Dundee DD195Y, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Fleming","sequence":"additional","affiliation":[{"name":"Departments of Genetics, Biochemistry, and Medical Genetics, University of Cambridge, Cambridge CB2 1TN, United Kingdom; Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, London 5W17 ORE, United Kingdom; and Department of Molecular and Cellular Pathology, University of Dundee, Dundee DD195Y, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Brindle","sequence":"additional","affiliation":[{"name":"Departments of Genetics, Biochemistry, and Medical Genetics, University of Cambridge, Cambridge CB2 1TN, United Kingdom; Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, London 5W17 ORE, United Kingdom; and Department of Molecular and Cellular Pathology, University of Dundee, Dundee DD195Y, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sandford","sequence":"additional","affiliation":[{"name":"Departments of Genetics, Biochemistry, and Medical Genetics, University of Cambridge, Cambridge CB2 1TN, United Kingdom; Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, London 5W17 ORE, United Kingdom; and Department of Molecular and Cellular Pathology, University of Dundee, Dundee DD195Y, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,10,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00370.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1993.17"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(96)90378-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2071"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.406"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5266.1339"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-151"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35050128"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.8.4947"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.11.6013"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00123-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V115814"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.1.F17"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1211"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119090"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V84616"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.12.6397"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401654"},{"key":"e_1_3_3_19_2","first-page":"221","volume":"75","author":"Peters D J","year":"1996","unstructured":"D J Peters, L Spruit, R Klingel, F Prins, H J Baelde, P C Giordano, L F Bernini, E de Heer, M H Breuning, J A Bruijn Lab Invest 75, 221\u2013230 (1996).","journal-title":"Lab Invest"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199904)214:4<337::AID-AJA6>3.0.CO;2-O"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00257-4"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.4.1524"},{"key":"e_1_3_3_23_2","first-page":"F602","volume":"272","author":"Van Adelsberg J","year":"1997","unstructured":"J Van Adelsberg, S Chamberlain, V D'Agati Am J Physiol 272, F602\u2013F609 (1997).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040550097"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1097-179"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81570-6"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/71724"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.18.2617"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.10.4303"},{"key":"e_1_3_3_30_2","first-page":"113","volume-title":"Teratocarcinoms and embryonic stem cells. 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