Absence of radius and ulna in mice lacking hoxa-11 andhoxd-11

Allan Peter Davis, David P. Witte, Hsiu M. Hsieh-Li, S. Steven Potter, Mario R. Capecchi*


研究成果: 雜誌貢獻期刊論文同行評審

514 引文 斯高帕斯(Scopus)


MICE with targeted disruptions1 in Hoxgenes 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 (Hox9-13) pattern the posterior region of the vertebrate embryo and the appendicular skeleton4-18. Mice with individual mutations in the paralogous genes hoxa-11 and hoxd-11 have been described15-18. 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 Hoxgenes function together to specify limb outgrowth and patterning along the proximodistal axis.

頁(從 - 到)791-795
出版狀態已發佈 - 1995 6月

ASJC Scopus subject areas

  • 多學科


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