A mouse model of greig cephalopolysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene

Nat Genet. 1993 Mar;3(3):241-6. doi: 10.1038/ng0393-241.


Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development. Recently, the human GLI3 gene has been proposed to be a candidate gene for GCPS. Here we describe the molecular characterization of extra-toes (Xt), which is a mouse model of GCPS. The Xt heterozygotes show craniofacial defects and a polydactyly phenotype similar to GCPS. We show that a deficiency of Gli3 expression in the XtJ mutant is due to a deletion within the 3' end of the gene. Furthermore, structures affected in the mouse mutant and human syndrome were found to correlate with expression domains of Gli3 in mouse. These results strongly suggest that the deficiency of GLI3 function leads to GCPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Blotting, Southern
  • DNA / genetics
  • DNA / isolation & purification
  • Disease Models, Animal
  • Embryo, Mammalian / pathology
  • Facial Bones / abnormalities*
  • Facial Bones / embryology
  • Gene Deletion*
  • Homozygote
  • Humans
  • Introns*
  • Mice
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • Phenotype
  • Skull / abnormalities*
  • Skull / embryology
  • Syndactyly / embryology
  • Syndactyly / genetics*
  • Syndrome


  • DNA