{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:20:51Z","timestamp":1760487651474,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,1,31]],"date-time":"2007-01-31T00:00:00Z","timestamp":1170201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gli3 protein processing to generate the Gli3 repressor is mediated by proteasome and inhibited by Hedgehog signaling. The Gli3 repressor concentration is graded along the anterior\u2013posterior axis of the developing vertebrate limb due to posteriorly restricted Sonic hedgehog expression. In this study, we created a small deletion at the Gli3 locus (<jats:italic>Gli3<\/jats:italic><jats:sup>\u0394<jats:italic>68<\/jats:italic><\/jats:sup>), which causes a half reduction in the Gli3 repressor levels and a slightly increased activity of full\u2010length mutant protein in the limb. Mice homozygous for <jats:italic>Gli3<\/jats:italic><jats:sup>\u0394<jats:italic>68<\/jats:italic><\/jats:sup> develop one to two extra partial digits in the anterior of the limb, while mice carrying one copy of the <jats:italic>Gli3<\/jats:italic><jats:sup>\u0394<jats:italic>68<\/jats:italic><\/jats:sup> allele die soon after birth and display seven digits. These phenotypes are more severe than those found in mice lacking one wild\u2010type <jats:italic>Gli3<\/jats:italic> allele. The expression of <jats:italic>dHand<\/jats:italic>, <jats:italic>Hoxd12<\/jats:italic>, and <jats:italic>Hoxd13<\/jats:italic> is anteriorly expanded in the limb, even though no up\u2010regulation of <jats:italic>Gli1<\/jats:italic> and <jats:italic>Ptc<\/jats:italic> RNA expression is detected. These findings suggest that a decrease in the Gli3 repressor level in combination with an increase in Gli3 full\u2010length activity results in more severe digit patterning abnormalities than those caused by a loss of one wild\u2010type <jats:italic>Gli3<\/jats:italic> allele. Developmental Dynamics 236:769\u2013776, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.21082","type":"journal-article","created":{"date-parts":[[2007,2,2]],"date-time":"2007-02-02T23:14:22Z","timestamp":1170458062000},"page":"769-776","source":"Crossref","is-referenced-by-count":22,"title":["A hypermorphic mouse Gli3 allele results in a polydactylous limb 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