Iris hypoplasia in mice that lack the alternatively spliced Pax6(5a) isoform

Proc Natl Acad Sci U S A. 2002 May 14;99(10):6812-5. doi: 10.1073/pnas.102691299. Epub 2002 Apr 30.


PAX6 is an evolutionarily conserved transcription factor that plays a critical role in vertebrate and invertebrate eye formation. Heterozygous null mutations in the PAX6 gene result in aniridia in humans and a distinct small eye syndrome in rodents. Vertebrates primarily express two alternatively spliced isoforms of Pax6 that differ by the presence or absence of exon 5a (e5A) that encodes an additional 14 aa residues within the paired domain. The e5a-containing isoform, PAX6(5a), is specific to and conserved in vertebrates. To determine the role of PAX6(5a), we have generated mice that lack e5a of the Pax6 gene. Unlike Pax6 null mice that exhibit anopthalmia with central nervous system defects and lethality, 5a isoform-null mice have iris hypoplasia and defects in the cornea, lens, and retina. Although invertebrates have structures that respond to light intensity and act to restrict light exposure of the eyes, a significant and distinct feature of the vertebrate eye is its ability to regulate the amount of incoming light through contractile pupils. This feature of the eye not only allows vertebrates to see in various light conditions but also enhances image resolution. The requirement of the 5a isoform in iris formation suggests that the evolution of this isoform contributed to advanced features of the vertebrate eye.

Publication types

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

MeSH terms

  • Alternative Splicing*
  • Animals
  • Cornea / pathology
  • Eye Proteins / genetics
  • Eye Proteins / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Iris / abnormalities*
  • Iris / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Repressor Proteins
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Protein Isoforms
  • Repressor Proteins
  • Transcription Factors