The zebrafish merovingian mutant reveals a role for pH regulation in hair cell toxicity and function

Stawicki, T.M., Owens, K.N., Linbo, T., Reinhart, K.E., Rubel, E.W., Raible, D.W.
Disease models & mechanisms   7: 847-856 (Journal)
Registered Authors
Linbo, Tor, Owens, Kelly, Raible, David, Stawicki, Tamara
Aminoglycosides, Cisplatin, H+-ATPase, Hair cells, Ototoxicity, pH
MeSH Terms
  • Acids/metabolism
  • Amino Acid Sequence
  • Animals
  • Cisplatin/toxicity
  • DNA-Binding Proteins/chemistry
  • DNA-Binding Proteins/genetics*
  • DNA-Binding Proteins/metabolism
  • Extracellular Space/drug effects
  • Extracellular Space/metabolism
  • Hair Cells, Auditory, Inner/drug effects
  • Hair Cells, Auditory, Inner/enzymology
  • Hair Cells, Auditory, Inner/metabolism*
  • Hair Cells, Auditory, Inner/pathology*
  • Hydrogen-Ion Concentration
  • Molecular Sequence Data
  • Mutation, Missense/genetics
  • Neomycin/toxicity
  • Proton-Translocating ATPases/metabolism
  • Pyridinium Compounds/metabolism
  • Quaternary Ammonium Compounds/metabolism
  • Transcription Factors/chemistry
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Zebrafish/genetics*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
24973752 Full text @ Dis. Model. Mech.
Control of the extracellular environment of inner ear hair cells by ionic transporters is crucial for hair cell function. In addition to inner ear hair cells, aquatic vertebrates have hair cells on the surface of their body in the lateral line system. The ionic environment of these cells also appears to be regulated, although the mechanisms of this regulation are less understood than those of the mammalian inner ear. We identified the merovingian mutant through genetic screening in zebrafish for genes involved in drug-induced hair cell death. Mutants show complete resistance to neomycin-induced hair cell death and partial resistance to cisplatin-induced hair cell death. This resistance is probably due to impaired drug uptake as a result of reduced mechanotransduction ability, suggesting that the mutants have defects in hair cell function independent of drug treatment. Through genetic mapping we found that merovingian mutants contain a mutation in the transcription factor gcm2. This gene is important for the production of ionocytes, which are cells crucial for whole body pH regulation in fish. We found that merovingian mutants showed an acidified extracellular environment in the vicinity of both inner ear and lateral line hair cells. We believe that this acidified extracellular environment is responsible for the defects seen in hair cells of merovingian mutants, and that these mutants would serve as a valuable model for further study of the role of pH in hair cell function.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes