Mouse model of split hand/foot malformation type I

Genesis. 2002 Jun;33(2):97-101. doi: 10.1002/gene.10098.


Split hand/foot malformation type I (SHFM1) disease locus maps to chromosome 7q21.3-q22, a region that includes the distal-less-related (dll) genes DLX5 and DLX6. However, incomplete penetrance, variable expressivity, segregation distortion, and syndromic association with other anomalies have so far prevented the identification of the SHFM1 gene(s) in man. Here we show that the targeted double inactivation of Dlx5 and Dlx6 in the mouse causes in homozygous mutant animals bilateral ectrodactyly with a severe defect of the central ray of the hindlimbs, a malformation typical of SHFM1. This is the first evidence that the role of dll/Dlx genes in appendage development is conserved from insects to mammals and proves their involvement in SHFM1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Gene Deletion
  • Homeodomain Proteins / genetics
  • Humans
  • Limb Deformities, Congenital / genetics*
  • Mice
  • Physical Chromosome Mapping
  • Transcription Factors


  • DLX5 protein, human
  • DLX6 protein, human
  • Dlx5 protein, mouse
  • Dlx6 protein, mouse
  • Homeodomain Proteins
  • Transcription Factors