The zebrafish shocked gene encodes a glycine transporter and is essential for the function of early neural circuits in the CNS

Cui, W.W., Low, S.E., Hirata, H., Saint-Amant, L., Geisler, R., Hume, R.I., and Kuwada, J.Y.
The Journal of neuroscience : the official journal of the Society for Neuroscience   25(28): 6610-6620 (Journal)
Registered Authors
Cui, Wilson, Geisler, Robert, Hirata, Hiromi, Kuwada, John, Low, Sean, Saint-Amant, Louis
behavior; zebrafish; mutation; glycine transporter; behavior; strychnine
MeSH Terms
  • Animals
  • Central Nervous System/embryology*
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/pathology
  • Embryo, Nonmammalian/physiopathology
  • Extracellular Fluid/metabolism
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Glycine/metabolism*
  • Glycine Plasma Membrane Transport Proteins/antagonists & inhibitors
  • Glycine Plasma Membrane Transport Proteins/deficiency
  • Glycine Plasma Membrane Transport Proteins/genetics
  • Glycine Plasma Membrane Transport Proteins/physiology*
  • Muscles/embryology
  • Muscles/physiology
  • Mutation, Missense
  • Nerve Tissue Proteins/antagonists & inhibitors
  • Nerve Tissue Proteins/deficiency
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/physiology*
  • Oocytes
  • Phenotype
  • Physical Stimulation
  • RNA, Messenger/biosynthesis
  • RNA, Messenger/genetics
  • RNA, Messenger/pharmacology
  • Recombinant Fusion Proteins/metabolism
  • Rhombencephalon/embryology
  • Rhombencephalon/metabolism
  • Sarcosine/analogs & derivatives
  • Sarcosine/pharmacology
  • Spinal Cord/embryology
  • Spinal Cord/metabolism
  • Swimming
  • Xenopus
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
16014722 Full text @ J. Neurosci.
shocked (sho) is a zebrafish mutation that causes motor deficits attributable to CNS defects during the first 2d of development. Mutant embryos display reduced spontaneous coiling of the trunk, diminished escape responses when touched, and an absence of swimming. A missense mutation in the slc6a9 gene that encodes a glycine transporter (GlyT1) was identified as the cause of the sho phenotype. Antisense knock-down of GlyT1 in wild-type embryos phenocopies sho, and injection of wild-type GlyT1 mRNA into mutants rescues them. A comparison of glycine-evoked inward currents in Xenopus oocytes expressing either the wild-type or mutant protein found that the missense mutation results in a nonfunctional transporter. glyt1 and the related glyt2 mRNAs are expressed in the hindbrain and spinal cord in nonoverlapping patterns. The fact that these regions are known to be required for generation of early locomotory behaviors suggests that the regulation of extracellular glycine levels in the CNS is important for proper function of neural networks. Furthermore, physiological analysis after manipulation of glycinergic activity in wild-type and sho embryos suggests that the mutant phenotype is attributable to elevated extracellular glycine within the CNS.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes