A double-deletion mutation in the Pitx3 gene causes arrested lens development in aphakia mice

Genomics. 2001 Feb 15;72(1):61-72. doi: 10.1006/geno.2000.6464.


The recessive aphakia (ak) mouse mutant is characterized by bilateral microphthalmia due to a failure of lens morphogenesis. We fine-mapped the ak locus to the interval between D19Umi1 and D19Mit9, developed new polymorphic markers, and mapped candidate genes by construction of a BAC contig. The Pitx3 gene, known to be expressed in lens primordia, shows zero recombination with the ak mutation on our intersubspecific intercross panel representing 1170 meioses. A recent report described a deletion in the intergenic region between Gbf1 and Pitx3 as the possible ak mutation. Our results differ in that we find not only the distant intergenic deletion, but also a much larger deletion directly in the Pitx3 gene, eliminating exon 1 and extending into intron 1 and the promoter region. Pitx3 transcript levels are severely reduced in ak/ak mice from E11.5 to newborn (5 +/- 1% of the wildtype levels at E13.5), while an involvement of the flanking Gbf1 and Cig30 genes in the aberrant lens development is highly unlikely based on expression analysis. We conclude that the ak mutation consists of two deletions, the larger of which removes part of Pitx3, indicating a crucial role of this gene in early lens development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases
  • Animals
  • Aphakia / genetics*
  • Chromosome Mapping*
  • Chromosomes, Artificial, Bacterial
  • Chromosomes, Artificial, Yeast
  • Contig Mapping*
  • Crosses, Genetic
  • Exons
  • Fatty Acid Elongases
  • Female
  • Gene Expression
  • Guanine Nucleotide Exchange Factors / genetics
  • Homeodomain Proteins / genetics*
  • Introns
  • Lens, Crystalline / embryology*
  • Male
  • Membrane Proteins / genetics
  • Mice
  • Mutation
  • Nuclear Proteins*
  • Paired Box Transcription Factors
  • Polymerase Chain Reaction
  • Sequence Deletion*
  • Transcription Factors / genetics*


  • GBF1 protein, human
  • Guanine Nucleotide Exchange Factors
  • Homeodomain Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Paired Box Transcription Factors
  • Transcription Factors
  • homeobox protein PITX1
  • homeobox protein PITX3
  • homeobox protein PITX2
  • Acetyltransferases
  • Fatty Acid Elongases