{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T09:58:44Z","timestamp":1778234324226,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T00:00:00Z","timestamp":1296691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Polydactyly is a common malformation and can be an isolated anomaly or part of a pleiotropic syndrome. The elucidation of the mutated genes that cause polydactyly provides insight into limb development pathways. The extra\u2010toes spotting (\n                    <jats:italic>Xs<\/jats:italic>\n                    ) mouse phenotype manifests anterior polydactyly, predominantly in the fore\u2010limbs, with ventral hypopigmenation. The mapping of\n                    <jats:italic>\n                      Xs\u2010\n                      <jats:sup>J<\/jats:sup>\n                    <\/jats:italic>\n                    to chromosome 7 was confirmed, and the interval was narrowed to 322 kb using intersubspecific crosses. Two mutations were identified in eukaryotic translation initiation factor 3 subunit C (\n                    <jats:italic>Eif3c<\/jats:italic>\n                    ). An\n                    <jats:italic>Eif3c<\/jats:italic>\n                    c.907C&gt;T mutation (p.Arg303X) was identified in\n                    <jats:italic>\n                      Xs\n                      <jats:sup>J<\/jats:sup>\n                    <\/jats:italic>\n                    , and a c.1702_1758del mutation (p.Leu568_Leu586del) was identified in extra\u2010toes spotting\u2010like (\n                    <jats:italic>Xsl<\/jats:italic>\n                    ), an allele of\n                    <jats:italic>\n                      Xs\n                      <jats:sup>J<\/jats:sup>\n                      .\n                    <\/jats:italic>\n                    The effect of the\n                    <jats:italic>\n                      Xs\n                      <jats:sup>J<\/jats:sup>\n                    <\/jats:italic>\n                    mutation on the SHH\/GLI3 pathway was analyzed by\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization analysis, and we show that\n                    <jats:italic>Xs<\/jats:italic>\n                    mouse embryos have ectopic\n                    <jats:italic>Shh<\/jats:italic>\n                    and\n                    <jats:italic>Ptch1<\/jats:italic>\n                    expression in the anterior limb. In addition, anterior limb buds show aberrant\n                    <jats:italic>Gli3<\/jats:italic>\n                    processing, consistent with perturbed SHH\/GLI3 signaling. Based on the occurrence of\n                    <jats:italic>Eif3c<\/jats:italic>\n                    mutations in 2\n                    <jats:italic>Xs<\/jats:italic>\n                    lines and haploinsufficiency of the\n                    <jats:italic>\n                      Xs\n                      <jats:sup>J<\/jats:sup>\n                    <\/jats:italic>\n                    allele, we conclude that the\n                    <jats:italic>Xs<\/jats:italic>\n                    phenotype is caused by a mutation in\n                    <jats:italic>Eif3c<\/jats:italic>\n                    , a component of the translation initiation complex, and that the phenotype is associated with aberrant SHH\/GLI3 signaling.\u2014Gildea, D. E., Luetkemeier, E. S., Bao, X., Loftus, S. K., Mackem, S., Yang, Y., Pavan, W. J., Biesecker, L. G. The pleiotropic mouse phenotype extra\u2010toes spotting is caused by translation initiation factor\n                    <jats:italic>Eif3c<\/jats:italic>\n                    mutations and is associated with disrupted sonic hedgehog signaling.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 1596\u20131605 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-169771","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T22:56:19Z","timestamp":1296773779000},"page":"1596-1605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The pleiotropic mouse phenotype extra\u2010toes spotting is caused by translation initiation factor\n                    <i>Eif3c<\/i>\n                    mutations and is associated with disrupted sonic hedgehog signaling"],"prefix":"10.1096","volume":"25","author":[{"given":"Derek E.","family":"Gildea","sequence":"first","affiliation":[{"name":"Institute for Biomedical Sciences George Washington University Washington District of Columbia USA"},{"name":"National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin S.","family":"Luetkemeier","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaozhong","family":"Bao","sequence":"additional","affiliation":[{"name":"National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacie K.","family":"Loftus","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Mackem","sequence":"additional","affiliation":[{"name":"National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingzi","family":"Yang","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Pavan","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie G.","family":"Biesecker","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,2,3]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"158","article-title":"Extra-toes spotting, a newpolydactylymutation","volume":"83","author":"Lyon M.","year":"1989","journal-title":"Mouse News Letter"},{"key":"e_1_2_6_3_1","unstructured":"Ko V.(1998)A genomics approach to the study of mouse limb development: mapping of CA150 and the genetics of extra\u2010toes spotting.Undergraduate thesis Princeton University Princeton NJ USA"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0393-241"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-001-2115-X"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00356157"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320310411"},{"key":"e_1_2_6_8_1","first-page":"543","article-title":"Extra-toes: a new mutant gene causing multiple abnormalities in the mouse","volume":"17","author":"Johnson D. 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