{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:26:47Z","timestamp":1781105207993,"version":"3.54.1"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"32","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,8,8]]},"abstract":"\n A recently promoted genome evolution model posits that mammalian pseudogenes can regulate their founding source genes, and it thereby ascribes an important function to \u201cjunk DNA.\u201d This model arose from analysis of a serendipitous mouse mutant in which a transgene insertion\/deletion caused severe polycystic kidney disease and osteogenesis imperfecta with \u224880% perinatal lethality, when inherited paternally [Hirotsune, S.,\n et al<\/jats:italic>\n . (2003)\n Nature<\/jats:italic>\n 423, 91\u201396]. The authors concluded that the transgene reduced the expression of a nearby transcribed and imprinted pseudogene,\n Mkrn1-p1<\/jats:italic>\n . This reduction in chromosome 5-imprinted\n Mkrn1-p1<\/jats:italic>\n transcripts was proposed to destabilize the cognate chromosome 6\n Mkrn1<\/jats:italic>\n source gene mRNA, with a partial reduction in one\n Mkrn1<\/jats:italic>\n isoform leading to the imprinted phenotype. Here, we show that 5\u2019\n Mkrn1-p1<\/jats:italic>\n is fully methylated on both alleles, a pattern indicative of silenced chromatin, and that\n Mkrn1-p1<\/jats:italic>\n is not transcribed and therefore cannot stabilize\n Mkrn1<\/jats:italic>\n transcripts in trans. A small, truncated, rodent-specific\n Mkrn1<\/jats:italic>\n transcript explains the product erroneously attributed to\n Mkrn1-p1<\/jats:italic>\n . Additionally,\n Mkrn1<\/jats:italic>\n expression is not imprinted, and 5\u2019\n Mkrn1<\/jats:italic>\n is fully unmethylated. Finally, mice in which\n Mkrn1<\/jats:italic>\n has been directly disrupted show none of the phenotypes attributed to a partial reduction of\n Mkrn1<\/jats:italic>\n . These data contradict the previous suggestions that\n Mkrn1-p1<\/jats:italic>\n is imprinted, and that either it or its source\n Mkrn1<\/jats:italic>\n gene relates to the original imprinted transgene phenotype. This study invalidates the data upon which the pseudogene trans-regulation model is based and therefore strongly supports the view that mammalian pseudogenes are evolutionary relics.\n <\/jats:p>","DOI":"10.1073\/pnas.0602216103","type":"journal-article","created":{"date-parts":[[2006,8,2]],"date-time":"2006-08-02T14:54:07Z","timestamp":1154530447000},"page":"12039-12044","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["The putatively functional\n Mkrn1-p1<\/i>\n pseudogene is neither expressed nor imprinted, nor does it regulate its source gene in trans"],"prefix":"10.1073","volume":"103","author":[{"given":"Todd A.","family":"Gray","sequence":"first","affiliation":[{"name":"*Wadsworth Center, David Axelrod Institute, Albany, NY 12208; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Wilson","sequence":"additional","affiliation":[{"name":"*Wadsworth Center, David Axelrod Institute, Albany, NY 12208; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Fortin","sequence":"additional","affiliation":[{"name":"*Wadsworth Center, David Axelrod Institute, Albany, NY 12208; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Birth Defects Laboratories, Division of Medical Genetics, Department of Pediatrics, Children's Hospital of Pittsburgh, and"},{"name":"Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,8,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2003.10.013"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2004.06.003"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2003.12.005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2004.01.007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401130101"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01535"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/423026a"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msh230"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-004-0550-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20084"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1321"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.03.117"},{"key":"e_1_3_3_13_2","first-page":"26","volume":"289","author":"Gibbs W. 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