{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:26:42Z","timestamp":1781108802641,"version":"3.54.1"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,11,24]]},"abstract":"<jats:p>\n                    Mouse models show that congenital neural tube defects (NTDs) can occur as a result of mutations in the platelet-derived growth factor receptor-\u03b1 gene (\n                    <jats:italic>PDGFR<\/jats:italic>\n                    \u03b1). Mice heterozygous for the\n                    <jats:italic>PDGFR<\/jats:italic>\n                    \u03b1-mutation\n                    <jats:italic>Patch<\/jats:italic>\n                    , and at the same time homozygous for the\n                    <jats:italic>undulated<\/jats:italic>\n                    mutation in the\n                    <jats:italic>Pax1<\/jats:italic>\n                    gene, exhibit a high incidence of lumbar spina bifida occulta, suggesting a functional relation between PDGFR\u03b1 and Pax1. Using the human\n                    <jats:italic>PDGFR\u03b1<\/jats:italic>\n                    promoter linked to a luciferase reporter, we show in the present paper that Pax1 acts as a transcriptional activator of the\n                    <jats:italic>PDGFR\u03b1<\/jats:italic>\n                    gene in differentiated Tera-2 human embryonal carcinoma cells. Two mutant Pax1 proteins carrying either the\n                    <jats:italic>undulated<\/jats:italic>\n                    -mutation or the Gln \u2192 His mutation previously identified by us in the\n                    <jats:italic>PAX1<\/jats:italic>\n                    gene of a patient with spina bifida, were not or less effective, respectively. Surprisingly, Pax1 mutant proteins appear to have opposing transcriptional activities in undifferentiated Tera-2 cells as well as in the U-2 OS osteosarcoma cell line. In these cells, the mutant Pax1 proteins enhance PDGFR\u03b1-promoter activity whereas the wild-type protein does not. The apparent up-regulation of PDGFR\u03b1 expression in these cells clearly demonstrates a gain-of-function phenomenon associated with mutations in Pax genes. The altered transcriptional activation properties correlate with altered protein\u2013DNA interaction in band-shift assays. Our data provide additional evidence that mutations in Pax1 can act as a risk factor for NTDs and suggest that the\n                    <jats:italic>PDGFR\u03b1<\/jats:italic>\n                    gene is a direct target of Pax1. In addition, the results support the hypothesis that deregulated PDGFR\u03b1 expression may be causally related to NTDs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.24.14459","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"14459-14463","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":21,"title":["Altered regulation of platelet-derived growth factor receptor-\u03b1 gene-transcription\n                    <i>in vitro<\/i>\n                    by spina bifida-associated mutant Pax1 proteins"],"prefix":"10.1073","volume":"95","author":[{"given":"Paul H. L. J.","family":"Joosten","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans A.","family":"Hol","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E. C.","family":"van Beersum","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben C. J.","family":"Hamel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs B.","family":"Afink","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everardus J. J.","family":"van Zoelen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin C. M.","family":"Mariman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands; Institute Mammalian Genetics, GSF-National Research, Center for Environment and Health, 85764 Neuherberg, Germany; Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; and Department of Pathology, University Hospital, Uppsala University, S-75185 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,11,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199709)56:3<177::AID-TERA1>3.0.CO;2-Z"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-437X(94)90032-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03490.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(05)80177-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90039-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90434-Z"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.5.1109"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.1996.0018"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0995-60"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.8.655"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.1.6"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199705)209:1<105::AID-AJA10>3.0.CO;2-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.14.2691"},{"key":"e_1_3_3_14_2","first-page":"1667","volume":"10","author":"Afink G B","year":"1995","unstructured":"G B Afink, M Nister, B H G J Stassen, P H L J Joosten, P J H Rademakers, E Bongcam-Rudloff, E J J Van Zoelen Oncogene 10, 1667\u20131672 (1995).","journal-title":"Oncogene"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00190-1"},{"key":"e_1_3_3_16_2","volume-title":"Antibodies: A Laboratory Manual","author":"Harlow E","year":"1988","unstructured":"E Harlow, D Lane Antibodies: A Laboratory Manual (Cold Spring Harbor Lab. 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