Mutation of the zebrafish choroideremia gene encoding Rab escort protein 1 devastates hair cells

Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2572-7. doi: 10.1073/pnas.0308474100.


To identify genes important for hair-cell function, we conducted a mutagenic screen in zebrafish. Larvae from one mutant line, ru848, were unresponsive to acoustic stimuli and unable to balance. The mutation results in a 90% reduction in hair-cell number and partial retinal degeneration by 5 days postfertilization. We localized the recessive ru848 mutation by positional cloning to the zebrafish homolog of the human Choroideremia gene, which encodes Rab escort protein 1. This protein is essential for the normal prenylation of Rabs. Mutations in the human gene induce choroideremia, a disease marked by slow-onset degeneration of rod photoreceptors and retinal pigment epithelial cells. The degenerative phenotype resulting from a null mutation in the zebrafish gene indicates that hair cells and retinal cells require Rab escort protein 1 for survival.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Alkyl and Aryl Transferases / genetics*
  • Amino Acid Sequence
  • Animals
  • Cell Survival
  • Cloning, Molecular
  • Conserved Sequence
  • Crosses, Genetic
  • Ear, Inner / physiology
  • Embryo, Nonmammalian / physiology
  • Genes, Recessive
  • Hair Cells, Auditory / cytology*
  • Heterozygote
  • Larva
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Retina / cytology
  • Sequence Alignment
  • Zebrafish / genetics*
  • Zebrafish / growth & development
  • Zebrafish Proteins


  • Adaptor Proteins, Signal Transducing
  • Zebrafish Proteins
  • chm protein, zebrafish
  • Alkyl and Aryl Transferases