TY - JOUR T1 - The Zebrafish <em>shocked</em> Gene Encodes a Glycine Transporter and Is Essential for the Function of Early Neural Circuits in the CNS JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6610 LP - 6620 DO - 10.1523/JNEUROSCI.5009-04.2005 VL - 25 IS - 28 AU - Wilson W. Cui AU - Sean E. Low AU - Hiromi Hirata AU - Louis Saint-Amant AU - Robert Geisler AU - Richard I. Hume AU - John Y. Kuwada Y1 - 2005/07/13 UR - http://www.jneurosci.org/content/25/28/6610.abstract N2 - 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 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. ER -