The ZebrafishshockedGene Encodes a Glycine Transporter and Is Essential for the Function of Early Neural Circuits in the CNS

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Abstract
shocked(sho) is a zebrafish mutation that causes motor deficits attributable to CNS defects during the first2dof development. Mutant embryos display reduced spontaneous coiling of the trunk, diminished escape responses when touched, and an absence of swimming. A missense mutation in theslc6a9gene that encodes a glycine transporter (GlyT1) was identified as the cause of theshophenotype. Antisense knock-down of GlyT1 in wild-type embryos phenocopiessho, and injection of wild-type GlyT1 mRNA into mutants rescues them. A comparison of glycine-evoked inward currents inXenopusoocytes expressing either the wild-type or mutant protein found that the missense mutation results in a nonfunctional transporter.glyt1and the relatedglyt2mRNAs 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 andshoembryos suggests that the mutant phenotype is attributable to elevated extracellular glycine within the CNS.