Zebrafish bandoneon mutants display behavioral defects due to a mutation in the glycine receptor β-subunit

Hirata, H., Saint-Amant, L., Downes, G.B., Cui, W.W., Zhou, W., Granato, M., and Kuwada, J.Y.
Proceedings of the National Academy of Sciences of the United States of America   102(23): 8345-8350 (Journal)
Registered Authors
Cui, Wilson, Downes, Gerald, Granato, Michael, Hirata, Hiromi, Kuwada, John, Saint-Amant, Louis, Zhou, Weibin
channel; synapse; hyperekplexia; strychnine
MeSH Terms
  • Animals
  • Behavior, Animal/physiology*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Molecular Sequence Data
  • Muscles/innervation
  • Muscles/physiology
  • Mutation/genetics*
  • Protein Subunits/genetics
  • Protein Subunits/metabolism
  • Receptors, Glycine/antagonists & inhibitors
  • Receptors, Glycine/chemistry*
  • Receptors, Glycine/genetics*
  • Rhombencephalon/metabolism
  • Spinal Cord/metabolism
  • Strychnine/pharmacology
  • Synaptic Transmission
  • Touch/physiology
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
15928085 Full text @ Proc. Natl. Acad. Sci. USA
Bilateral alternation of muscle contractions requires reciprocal inhibition between the two sides of the hindbrain and spinal cord, and disruption of this inhibition should lead to simultaneous activation of bilateral muscles. At 1 day after fertilization, wild-type zebrafish respond to mechanosensory stimulation with multiple fast alternating trunk contractions, whereas bandoneon (beo) mutants contract trunk muscles on both sides simultaneously. Similar simultaneous contractions are observed in wild-type embryos treated with strychnine, a blocker of the inhibitory glycine receptor (GlyR). This result suggests that glycinergic synaptic transmission is defective in beo mutants. Muscle voltage recordings confirmed that muscles on both sides of the trunk in beo are likely to receive simultaneous synaptic input from the CNS. Recordings from motor neurons revealed that glycinergic synaptic transmission was missing in beo mutants. Furthermore, immunostaining with an antibody against GlyR showed clusters in wild-type neurons but not in beo neurons. These data suggest that the failure of GlyRs to aggregate at synaptic sites causes impairment of glycinergic transmission and abnormal behavior in beo mutants. Indeed, mutations in the GlyR beta-subunit, which are thought to be required for proper localization of GlyRs, were identified as the basis for the beo mutation. These data demonstrate that GlyRbeta is essential for physiologically relevant clustering of GlyRs in vivo. Because GlyR mutations in humans lead to hyperekplexia, a motor disorder characterized by startle responses, the zebrafish beo mutant should be a useful animal model for this condition.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes