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Gene Review

Slc6a9  -  solute carrier family 6 (neurotransmitter...

Mus musculus

Synonyms: GlyT-1, GlyT1, Glyt-1, Glyt1, Sodium-and chloride-dependent glycine transporter 1, ...
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High impact information on Slc6a9

  • The analysis of GlyT knockout mice has revealed distinct functions of individual GlyT subtypes in synaptic transmission and provided animal models for two hereditary human diseases, glycine encephalopathy and hyperekplexia [1].
  • Conversely, glycine or the GlyT1 inhibitor sarcosine suppress respiratory activity in slices from wild-type mice [2].
  • Thus, reduced expression of GlyT1 enhances hippocampal NMDAR function and memory retention and protects against an amphetamine disruption of sensory gating, suggesting that drugs which inhibit GlyT1 might have both cognitive enhancing and antipsychotic effects [3].
  • To characterize further the role of GlyT1, we generated mice in which the gene encoding GlyT1 was inactivated by homologous recombination through insertion of a PGK-Neo cassette in place of exons 2 and 3 [3].
  • Both HMGN3a and HMGN3b upregulate the expression of the glycine transporter 1 gene (Glyt1) [4].

Biological context of Slc6a9

  • We observed faster decay kinetics, reduced ifenprodil sensitivity and increased zinc-induced antagonism in N-methyl-d-aspartate receptor (NMDAR) currents of GlyT1+/- mice [5].
  • To facilitate the morphological and functional analysis of glycinergic neurons, we generated bacterial artificial chromosome (BAC) transgenic mice, which specifically express enhanced green fluorescent protein (EGFP) under the control of the promotor of the glycine transporter (GlyT) 2 gene, which is a reliable marker for glycinergic neurons [6].
  • Both GlyT1 and GlyT2 are essential for CNS function, as revealed by the lethal phenotypes of the respective knockout mice [7].

Anatomical context of Slc6a9


Associations of Slc6a9 with chemical compounds

  • Glyt1 encodes a membrane transporter that regulates the glycine concentration in synaptic junctions [4].
  • The glial GlyT subtype GlyT1 is well located to activate NMDA receptors [11].
  • The AMPA receptor potentiator LY451646, iGlu5 kainate receptor antagonist LY382884, glycine(B) receptor partial agonist D: -cycloserine, and GlyT-1 inhibitor ORG-24461 were ineffective in this model [12].

Other interactions of Slc6a9


Analytical, diagnostic and therapeutic context of Slc6a9

  • Chromatin immunoprecipitation assays showed that HMGN3 protein is recruited to a region of the Glyt1 gene encompassing the Glyt1a transcriptional start site [4].
  • Real-time quantitative PCR revealed no transcripts in newborn homozygous [GlyT1(-/-)] mice and a 50% reduction in heterozygous (HZ) [GlyT1(+/-)] mice as compared with WT littermates [3].


  1. Glycine transporters: essential regulators of neurotransmission. Eulenburg, V., Armsen, W., Betz, H., Gomeza, J. Trends Biochem. Sci. (2005) [Pubmed]
  2. Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition. Gomeza, J., Hülsmann, S., Ohno, K., Eulenburg, V., Szöke, K., Richter, D., Betz, H. Neuron (2003) [Pubmed]
  3. Gene knockout of glycine transporter 1: characterization of the behavioral phenotype. Tsai, G., Ralph-Williams, R.J., Martina, M., Bergeron, R., Berger-Sweeney, J., Dunham, K.S., Jiang, Z., Caine, S.B., Coyle, J.T. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Chromosomal proteins HMGN3a and HMGN3b regulate the expression of glycine transporter 1. West, K.L., Castellini, M.A., Duncan, M.K., Bustin, M. Mol. Cell. Biol. (2004) [Pubmed]
  5. Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in mice. Martina, M., B-Turcotte, M.E., Halman, S., Tsai, G., Tiberi, M., Coyle, J.T., Bergeron, R. J. Physiol. (Lond.) (2005) [Pubmed]
  6. Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. Zeilhofer, H.U., Studler, B., Arabadzisz, D., Schweizer, C., Ahmadi, S., Layh, B., Bösl, M.R., Fritschy, J.M. J. Comp. Neurol. (2005) [Pubmed]
  7. Glycine transporters: essential regulators of synaptic transmission. Betz, H., Gomeza, J., Armsen, W., Scholze, P., Eulenburg, V. Biochem. Soc. Trans. (2006) [Pubmed]
  8. Gene structure and glial expression of the glycine transporter GlyT1 in embryonic and adult rodents. Adams, R.H., Sato, K., Shimada, S., Tohyama, M., Püschel, A.W., Betz, H. J. Neurosci. (1995) [Pubmed]
  9. Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile. Yee, B.K., Balic, E., Singer, P., Schwerdel, C., Grampp, T., Gabernet, L., Knuesel, I., Benke, D., Feldon, J., Mohler, H., Boison, D. J. Neurosci. (2006) [Pubmed]
  10. Characterization of an amacrine cell type of the mammalian retina immunoreactive for vesicular glutamate transporter 3. Haverkamp, S., Wässle, H. J. Comp. Neurol. (2004) [Pubmed]
  11. Bergmann glial GlyT1 mediates glycine uptake and release in mouse cerebellar slices. Huang, H., Barakat, L., Wang, D., Bordey, A. J. Physiol. (Lond.) (2004) [Pubmed]
  12. Pharmacological characterization of stress-induced hyperthermia in DBA/2 mice using metabotropic and ionotropic glutamate receptor ligands. Rorick-Kehn, L.M., Hart, J.C., McKinzie, D.L. Psychopharmacology (Berl.) (2005) [Pubmed]
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