Duplication of the Hoxd11 gene causes alterations in the axial and appendicular skeleton of the mouse

Dev Biol. 2002 Sep 1;249(1):96-107. doi: 10.1006/dbio.2002.0755.

Abstract

The Hox genes encode a group of transcription factors essential for proper development of the mouse. Targeted mutation of the Hoxd11 gene causes reduced male fertility, vertebral transformation, carpal bone fusions, and reductions in digit length. A duplication of the Hoxd11 gene was created with the expectation that the consequences of restricted overexpression in the appropriate cells would provide further insight into the function of the Hoxd11 gene product. Genetic assays demonstrated that two tandem copies of Hoxd11 were functionally indistinguishable from the normal two copies of the gene on separate chromosomes with respect to formation of the axial and appendicular skeleton. Extra copies of Hoxd11 caused an increase in the lengths of some bones of the forelimb autopod and a decrease in the number of lumbar vertebrae. Further, analysis of the Hoxd11 duplication demonstrated that the Hoxd11 protein can perform some functions supplied by its paralogue Hoxa11. For example, the defects in forelimb bones are corrected when extra copies of Hoxd11 are present in the Hoxa11 homozygous mutant background. Thus, it appears that Hoxd11 can quantitatively compensate for the absence of Hoxa11 protein, and therefore Hoxa11 and Hoxd11 are functionally equivalent in the zeugopod. However, extra copies of Hoxd11 did not improve male or female fertility in Hoxa11 mutants. Interestingly, the insertion of an additional Hoxd11 locus into the HoxD complex does not appear to affect the expression patterns of the neighboring Hoxd10, -d12, or -d13 genes.

MeSH terms

  • Animals
  • Bone Development / genetics
  • Bone and Bones / abnormalities*
  • Embryo, Mammalian
  • Female
  • Forelimb / embryology
  • Forelimb / growth & development
  • Gene Duplication*
  • Gene Expression Regulation, Developmental
  • Gene Order
  • Genetic Complementation Test
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Homozygote
  • Male
  • Mice
  • Mice, Mutant Strains
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Reproduction / genetics
  • Skeleton
  • Transcription Factors / genetics
  • Zebrafish Proteins*

Substances

  • Homeodomain Proteins
  • Hoxd10 protein, mouse
  • Hoxd12 protein, mouse
  • Hoxd13 protein, mouse
  • Hoxd4 protein, mouse
  • Oncogene Proteins
  • Tlx1 protein, mouse
  • Transcription Factors
  • Zebrafish Proteins
  • hoxd10a protein, zebrafish