Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality

Neuron. 2003 Nov 13;40(4):797-806. doi: 10.1016/s0896-6273(03)00673-1.


The glycine transporter subtype 2 (GlyT2) is localized in the axon terminals of glycinergic neurons. Mice deficient in GlyT2 are normal at birth but during the second postnatal week develop a lethal neuromotor deficiency that resembles severe forms of human hyperekplexia (hereditary startle disease) and is characterized by spasticity, tremor, and an inability to right. Histological and immunological analyses failed to reveal anatomical or biochemical abnormalities, but the amplitudes of glycinergic miniature inhibitory currents (mIPSCs) were strikingly reduced in hypoglossal motoneurons and dissociated spinal neurons from GlyT2-deficient mice. Thus, postnatal GlyT2 function is crucial for efficient transmitter loading of synaptic vesicles in glycinergic nerve terminals, and the GlyT2 gene constitutes a candidate disease gene in human hyperekplexia patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Neutral / deficiency*
  • Amino Acid Transport Systems, Neutral / genetics
  • Animals
  • Animals, Newborn
  • Brain Stem / growth & development
  • Brain Stem / metabolism*
  • Brain Stem / physiopathology
  • Disease Models, Animal
  • Fetus
  • Gene Deletion
  • Genes, Lethal / genetics*
  • Glycine / metabolism
  • Glycine Plasma Membrane Transport Proteins
  • Heredodegenerative Disorders, Nervous System / genetics*
  • Heredodegenerative Disorders, Nervous System / metabolism
  • Heredodegenerative Disorders, Nervous System / physiopathology
  • Hypoglossal Nerve / metabolism
  • Hypoglossal Nerve / physiopathology
  • Mice
  • Mice, Knockout
  • Motor Neurons / metabolism
  • Neural Inhibition / genetics
  • Organ Culture Techniques
  • Phenotype
  • Presynaptic Terminals / metabolism
  • Reflex, Startle / genetics*
  • Synaptic Transmission / genetics
  • Synaptic Vesicles / metabolism


  • Amino Acid Transport Systems, Neutral
  • Glycine Plasma Membrane Transport Proteins
  • Slc6a5 protein, mouse
  • Glycine