{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:18:30Z","timestamp":1790162310919,"version":"4.1.0"},"reference-count":52,"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":[[2002,10,15]]},"abstract":"<jats:p>\n                    In human diseases related to tumor-suppressor genes, it is suggested that only the complete loss of the protein results in specific symptoms such as tumor formation, whereas simple reduction of protein quantity to 50%, called haploinsufficiency, essentially does not affect cellular behavior. Using a model of gene expression, it was presumed that haploinsufficiency is related to an increased noise in gene expression also\n                    <jats:italic>in vivo<\/jats:italic>\n                    [Cook, D. L., Gerber, A. N. &amp; Tapscott, S. J. (1998)\n                    <jats:italic>Proc. Natl. Acad. Sci. USA<\/jats:italic>\n                    95, 15641\u201315646]. Here, we demonstrate that haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1 (\n                    <jats:italic>NF1<\/jats:italic>\n                    ) results in an increased variation of dendrite formation in cultured NF1 melanocytes. These morphological differences between NF1 and control melanocytes can be described by a mathematical model in which the cell is considered to be a self-organized automaton. The model describes the adjustment of the cells to a set point and includes a noise term that allows for stochastic processes. It describes the experimental data of control and NF1 melanocytes. In the cells haploinsufficient for\n                    <jats:italic>NF1<\/jats:italic>\n                    we found an altered signal-to-noise ratio detectable as increased variation in dendrite formation in two of three investigated morphological parameters. We also suggest that\n                    <jats:italic>in vivo<\/jats:italic>\n                    NF1 haploinsufficiency results in an increased noise in cellular regulation and that this effect of haploinsufficiency may be found also in other tumor suppressors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.212386999","type":"journal-article","created":{"date-parts":[[2002,10,15]],"date-time":"2002-10-15T12:43:03Z","timestamp":1034685783000},"page":"13783-13788","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["Increased noise as an effect of haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1\n                    <i>in vitro<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"Ralf","family":"Kemkemer","sequence":"first","affiliation":[{"name":"Departments of Biophysics and Human Genetics, University of Ulm, D-89070 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Schrank","sequence":"additional","affiliation":[{"name":"Departments of Biophysics and Human Genetics, University of Ulm, D-89070 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walther","family":"Vogel","sequence":"additional","affiliation":[{"name":"Departments of Biophysics and Human Genetics, University of Ulm, D-89070 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Gruler","sequence":"additional","affiliation":[{"name":"Departments of Biophysics and Human Genetics, University of Ulm, D-89070 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Departments of Biophysics and Human Genetics, University of Ulm, D-89070 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,10,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(98)01659-X"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)89009-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110057697"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040411297"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35014708"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/35066056"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5498.1968"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02738066"},{"key":"e_1_3_3_9_2","unstructured":"Gruler H. 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