{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:56:25Z","timestamp":1791266185919,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,7,8]]},"abstract":"<jats:p>\n                    To investigate the function of the Grb10 adapter protein, we have generated\n mice in which the\n                    <jats:italic>Grb10<\/jats:italic>\n                    gene was disrupted by a gene-trap insertion.\n Our experiments confirm that\n                    <jats:italic>Grb10<\/jats:italic>\n                    is subject to genomic imprinting\n with the majority of\n                    <jats:italic>Grb10<\/jats:italic>\n                    expression arising from the maternally\n inherited allele. Consistent with this, disruption of the maternal allele\n results in overgrowth of both the embryo and placenta such that mutant mice\n are at birth \u224830% larger than normal. This observation establishes that\n Grb10 is a potent growth inhibitor. In humans, GRB10 is located at chromosome\n 7p11.2\u2013p12 and has been associated with Silver\u2013Russell syndrome,\n in which \u224810% of those affected inherit both copies of chromosome 7 from\n their mother. Our results indicate that changes in GRB10 dosage could, in at\n least some cases, account for the severe growth retardation that is\n characteristic of Silver\u2013Russell syndrome. Because Grb10 is a signaling\n protein capable of interacting with tyrosine kinase receptors, we tested\n genetically whether\n                    <jats:italic>Grb10<\/jats:italic>\n                    might act downstream of insulin-like growth\n factor 2, a paternally expressed growth-promoting gene. The result indicates\n that\n                    <jats:italic>Grb10<\/jats:italic>\n                    action is essentially independent of insulin-like growth\n factor 2, providing evidence that imprinting acts on at least two major fetal\n growth axes in a manner consistent with parent\u2013offspring conflict\n theory.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1532175100","type":"journal-article","created":{"date-parts":[[2003,7,8]],"date-time":"2003-07-08T15:18:15Z","timestamp":1057677495000},"page":"8292-8297","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":242,"title":["Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism"],"prefix":"10.1073","volume":"100","author":[{"given":"Marika","family":"Charalambous","sequence":"first","affiliation":[{"name":"Developmental Biology Program and Centre for Regenerative Medicine,\r Department of Biology and Biochemistry, University of Bath, Claverton Down,\r Bath BA2 7AY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentia M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Developmental Biology Program and Centre for Regenerative Medicine,\r Department of Biology and Biochemistry, University of Bath, Claverton Down,\r Bath BA2 7AY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Developmental Biology Program and Centre for Regenerative Medicine,\r Department of Biology and Biochemistry, University of Bath, Claverton Down,\r Bath BA2 7AY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey E.","family":"Crew","sequence":"additional","affiliation":[{"name":"Developmental Biology Program and Centre for Regenerative Medicine,\r Department of Biology and Biochemistry, University of Bath, Claverton Down,\r Bath BA2 7AY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Developmental Biology Program and Centre for Regenerative Medicine,\r Department of Biology and Biochemistry, University of Bath, Claverton Down,\r Bath BA2 7AY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Ward","sequence":"additional","affiliation":[{"name":"Developmental Biology Program and Centre for Regenerative Medicine,\r Department of Biology and Biochemistry, University of Bath, Claverton Down,\r Bath BA2 7AY, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,6,26]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"1621","volume":"10","year":"1995","unstructured":"Ooi, J., Yajnik, V., Immanuel, D., Gordon, M., Moskow, J. J., Buchberg, A. M. & Margolis, B. (1995) Oncogene 10, 1621-1630.7731717","journal-title":"Oncogene"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.22.10287"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.37.22506"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119246"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.9.6217"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10475"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.4.979-991.2002"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.34.24094"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26382"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300033863"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.3.1102"},{"key":"e_1_3_2_12_2","first-page":"215","volume":"40","year":"1996","unstructured":"Jerome, C. A., Scherer, S. W., Tsui, L.-C., Gietz, R. D. & Triggs-Raine, B. (1996) Genomics 40, 215-216.","journal-title":"Genomics"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.12.810"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.11.1587"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5500"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(91)90040-W"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)28420-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4582"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/345078a0"},{"key":"e_1_3_2_20_2","first-page":"1079","volume":"130","year":"2003","unstructured":"Bennett, W. R., Crew, T. E., Slack, J. M. W. & Ward, A. (2003) Development (Cambridge, U.K.) 130, 1079-1088.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.7.1991"},{"key":"e_1_3_2_22_2","unstructured":"Sambrook J. Fritsch E. F. & Maniatis T. (1989) Molecular Cloning: A Laboratory Manual (Cold Spring\n Harbor Lab. Press Plainview NY)."},{"key":"e_1_3_2_23_2","first-page":"3621","volume":"124","year":"1997","unstructured":"Ainscough, J. F. X., Koide, T., Tada, M., Barton, S. & Surani, M. A. (1997) Development (Cambridge, U.K.) 124, 3621-3632.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.14.6592"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90513-X"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80085-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8666"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.101118898"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/84769"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061402"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192433399"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.295.5553.297"},{"key":"e_1_3_2_33_2","first-page":"1807","volume":"129","year":"2002","unstructured":"Lee, J., Inoue, K., Ono, R., Ogonuki, N., Khoda, T., Kaneko-Ishino, T., Ogura, A. & Ishino, F. (2002) Development (Cambridge, U.K.) 129, 1807-1817.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(00)00439-1"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/373699a0"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/376768a0"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0554"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1532175100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:21:52Z","timestamp":1649812912000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1532175100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,26]]},"references-count":37,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2003,7,8]]}},"alternative-id":["10.1073\/pnas.1532175100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1532175100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6,26]]},"assertion":[{"value":"2003-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}