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| ABSENCE OF RADIUS AND ULNA IN MICE LACKING HOXA-11 AND HOXD-11 |
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| Author(s): DAVIS AP, WITTE DP, HSIEHLI HM, POTTER SS, CAPECCHI MR |
| Source: NATURE Volume: 375 Issue: 6534 Pages: 791-795 Published: JUN 29 1995 |
| Times Cited: 326 References: 29 |
| Abstract: MICE with targeted disruptions(1) in Hox genes have been generated to evaluate the role of the Hox complex in determining the mammalian body plan. This complex of 38 genes encodes transcription factors that specify regional information along the embryonic axes. Early in vertebrate evolution an ancestral complex shared with invertebrates was duplicated twice to give rise to the four linkage groups (Hox A, B, C and D)(2,3). As a consequence, corresponding genes on the separate linkage groups, called paralogues, are most closely related to each other. Based on sequence similarities, the Hox genes have been subdivided into 13 paralogous groups. The five most 5' groups (Hox 9-13) pattern the posterior region of the vertebrate embryo and the appendicular skeleton(4-18). Mice with individual mutations in the paralogous genes hoxa-11 and hoxd-11 have been described(15-18). By breeding these two strains together we have generated double mutants which have dramatic phenotypes not apparent in mice homozygous for the individual mutations. The radius and the ulna of the forelimb are almost entirely eliminated, the axial skeleton shows homeotic transformations, and there are severe kidney defects not present in either single mutant. The limb and axial phenotypes are quantitative: as more mutant alleles are added to the genotype, the phenotype becomes progressively more severe. The appendicular skeleton defects suggest that paralogous Hox genes function together to specify limb outgrowth and patterning along the proximodistal axis. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV UTAH, SCH MED, HOWARD HUGHES MED INST, DEPT HUMAN GENET, SALT LAKE CITY, UT 84112 USA
2. UNIV CINCINNATI, COLL MED, DEPT PEDIAT, CINCINNATI, OH 45229 USA
3. UNIV CINCINNATI, COLL MED, CHILDRENS HOSP RES FDN, DIV BASIC SCI RES & PATHOL, CINCINNATI, OH 45229 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: RF989 |
| ISSN: 0028-0836 |
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