{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:30:11Z","timestamp":1791189011962,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,3,16]]},"abstract":"<jats:p>\n                    The Wilms tumor-suppressor gene,\n                    <jats:italic>WT1<\/jats:italic>\n                    , plays a key role in urogenital development, and WT1 dysfunction is implicated in both neoplastic (Wilms tumor, mesothelioma, leukemias, and breast cancer) and nonneoplastic (glomerulosclerosis) disease. The analysis of diseases linked specifically with\n                    <jats:italic>WT1<\/jats:italic>\n                    mutations, such as Denys\u2013Drash syndrome (DDS), can provide valuable insight concerning the role of WT1 in development and disease. DDS is a rare childhood disease characterized by a nephropathy involving mesangial sclerosis, XY pseudohermaphroditism, and\/or Wilms tumor (WT). DDS patients are constitutionally heterozygous for exonic point mutations in\n                    <jats:italic>WT1<\/jats:italic>\n                    , which include mutations predicted to truncate the protein within the C-terminal zinc finger (ZF) region. We report that heterozygosity for a targeted murine\n                    <jats:italic>Wt1<\/jats:italic>\n                    allele,\n                    <jats:italic>Wt1<\/jats:italic>\n                    <jats:sup>tmT396<\/jats:sup>\n                    , which truncates ZF3 at codon 396, induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice. Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event, implying a causal link between\n                    <jats:italic>Wt1<\/jats:italic>\n                    dysfunction and Wilms tumorigenesis in mice. However, the mutant WT1\n                    <jats:sup>tmT396<\/jats:sup>\n                    protein accounted for only 5% of WT1 in both heterozygous embryonic stem cells and the WT. This has implications regarding the mechanism by which the mutant allele exerts its effect.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.6.2931","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"2931-2936","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys\u2013Drash syndrome"],"prefix":"10.1073","volume":"96","author":[{"given":"Charles E.","family":"Patek","sequence":"first","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa H.","family":"Little","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Fleming","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Miles","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Charlieu","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Christie","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Doig","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Porteous","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Brookes","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L.","family":"Hooper","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 4072,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D.","family":"Hastie","sequence":"additional","affiliation":[{"name":"Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; Department of Pathology, The University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom; Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, 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