{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:27:53Z","timestamp":1782948473518,"version":"3.54.5"},"reference-count":44,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[1996,4,1]],"date-time":"1996-04-01T00:00:00Z","timestamp":828316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1996,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Using gene targeting in mice, we have undertaken a systematic mutational analysis of the homeobox-containing 5\u2032 HoxD genes. In particular, we have characterized the limb defects observed in mice with independent targeted disruptions of hoxd-12 and hoxd-13. Animals defective for hoxd-12 are viable, fertile, and appear outwardly normal yet have minor autopodal defects in the forelimb which include a reduction in the bone length of metacarpals and phalanges, and a malformation of the distal carpal bone d4. The limb phenotypes observed in hoxd-13 mutant mice are more extensive, including strong reductions in length, complete absences, or improper segmentations of many metacarpal and phalangeal bones. Additionally, the d4 carpal bone is not properly formed and often produces an extra rudimentary digit. To examine the genetic interactions between the 5\u2032 HoxD genes, we bred these mutant strains with each other and with our previously characterized hoxd-11 mouse to produce a series of trans-heterozygotes. Skeletal analyses of these mice reveal that these genes interact in the formation of the vertebrate limb, since the trans-heterozygotes display phenotypes not present in the individual heterozygotes, including more severe carpal, metacarpal and phalangeal defects. Some of these pheno- types appear to be accounted for by a delay in the ossification events in the autopod, which lead to either the failure of fusion or the elimination of cartilaginous elements. Characteristically, these mutations lead to the overall trun- cation of digits II and V on the forelimb. Additionally, some trans-animals show the growth of an extra postaxial digit VI, which is composed of a bony element resembling a phalange. The results demonstrate that these genes interact in the formation of the limb. In addition to the previously characterized paralogous interactions, a multitude of inter- actions between Hox genes is used to finely sculpt the forelimb. The 5\u2032 Hox genes could therefore act as a major permissive genetic milieu that has been exploited by evolutionary adaptation to form the tetrapod limbs.<\/jats:p>","DOI":"10.1242\/dev.122.4.1175","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T02:38:20Z","timestamp":1619404700000},"page":"1175-1185","source":"Crossref","is-referenced-by-count":190,"title":["A mutational analysis of the 5\u2032 <i>HoxD<\/i> genes: dissection of genetic interactions during limb development in the mouse"],"prefix":"10.1242","volume":"122","author":[{"given":"Allan Peter Davis and Mario R.","family":"Capecchi","sequence":"first","affiliation":[{"name":"University of Utah School of Medicine Howard Hughes Medical Institute, Department of Human Genetics , , Salt Lake City, Utah 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1996,4,1]]},"reference":[{"key":"2025021322455651800_DEVELOP_122_4_1175C1","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1126\/science.2660260","article-title":"Altering the genome by homologous recombination","volume":"244","author":"Capecchi","year":"1989","journal-title":"Science"},{"key":"2025021322455651800_DEVELOP_122_4_1175C2","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/0092-8674(95)90352-6","article-title":"Fibroblast growth factors induce additional limb development from the flank of chick embryos","volume":"80","author":"Cohn","year":"1995","journal-title":"Cell"},{"key":"2025021322455651800_DEVELOP_122_4_1175C3","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/370304a0","article-title":"Mice with targeted disruptions in the paralogous genes hoxa-3 and hoxd-3 reveal synergistic interactions","volume":"370","author":"Condie","year":"1994","journal-title":"Nature"},{"key":"2025021322455651800_DEVELOP_122_4_1175C4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/tera.1420310107","article-title":"Spontaneous and retinoic acid-induced postaxial polydactyly in mice","volume":"31","author":"Cusic","year":"1985","journal-title":"Teratology"},{"key":"2025021322455651800_DEVELOP_122_4_1175C5","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1242\/dev.120.8.2187","article-title":"Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11","volume":"120","author":"Davis","year":"1994","journal-title":"Development"},{"key":"2025021322455651800_DEVELOP_122_4_1175C6","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/375791a0","article-title":"Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11","volume":"375","author":"Davis","year":"1995","journal-title":"Nature"},{"key":"2025021322455651800_DEVELOP_122_4_1175C7","first-page":"2134","article-title":"Location of crossovers during gene targeting with insertion and replacement vectors","volume":"13","author":"Deng","year":"1993","journal-title":"Mol. 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