Mutation of the zebrafish choroideremia gene encoding Rab escort protein 1 devastates hair cells.
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.
Starr
Catherine J
CJ
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Kappler
James A
JA
Chan
Dylan K
DK
Kollmar
Richard
R
Hudspeth
A J
AJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D019883:Alkyl and Aryl Transferases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003433:Crosses, Genetic; D007758:Ear, Inner / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D005808:Genes, Recessive; D006198:Hair Cells, Auditory / Q000166:cytology*; D006579:Heterozygote; D007814:Larva; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000166:cytology; D016415:Sequence Alignment; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D029961:Zebrafish Proteins; C525249:chm protein, zebrafish; D019883:Alkyl and Aryl Transferases