The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene

Genesis. 2001 Sep;31(1):43-53. doi: 10.1002/gene.10003.


The eyeless inbred mouse strain ZRDCT has long served as a spontaneous model for human anophthalmia and the evolutionary reduction of eyes that has occurred in some naturally blind mammals. ZRDCT mice have orbits but lack eyes and optic tracts and have hypothalamic abnormalities. Segregation data suggest that a small number of interacting genes are responsible, including at least one major recessive locus, ey1. Although predicted since the 1940s, these loci were never identified. We mapped ey1 to chromosome 18 using an F2 genome scan and there found a Met10-->Leu mutation in Rx/rax, a homeobox gene that is expressed in the anterior headfold, developing retina, pineal, and hypothalamus and is translated via a leaky scanning mechanism. The mutation affects a conserved AUG codon that functions as an alternative translation initiation site and consequently reduces the abundance of Rx protein. In contrast to a targeted Rx null allele, which causes anophthalmia, central nervous system defects, and neonatal death, the hypomorphic M10L allele is fully viable.

Publication types

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

MeSH terms

  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Codon, Initiator / genetics*
  • DNA-Binding Proteins / genetics*
  • Drosophila Proteins*
  • Eye / embryology
  • Eye Proteins / genetics*
  • Female
  • Genotype
  • Homeodomain Proteins / genetics*
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Transcription Factors*
  • Xenopus laevis


  • Codon, Initiator
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Rax protein, mouse
  • Transcription Factors
  • ey protein, Drosophila

Associated data

  • GENBANK/AF001049
  • GENBANK/AF001906
  • GENBANK/AF001907
  • GENBANK/AF001908
  • GENBANK/AF001909
  • GENBANK/AF001910
  • GENBANK/AF017273
  • GENBANK/AF092538
  • GENBANK/AF115392
  • GENBANK/AF135839
  • GENBANK/AF264703
  • GENBANK/AF319461
  • GENBANK/AF319462
  • GENBANK/AF320224
  • GENBANK/AF320225
  • GENBANK/AJ007939
  • GENBANK/U73177