title: Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality.
abstract: 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.
authors: Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.
authors: Jesús
authors: J
authors: Gomeza
authors: Koji
authors: K
authors: Ohno
authors: Swen
authors: S
authors: Hülsmann
authors: Wencke
authors: W
authors: Armsen
authors: Volker
authors: V
authors: Eulenburg
authors: Diethelm W
authors: DW
authors: Richter
authors: Bodo
authors: B
authors: Laube
authors: Heinrich
authors: H
authors: Betz
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005333:Fetus; D017353:Gene Deletion; D005804:Genes, Lethal / Q000235:genetics*; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007002:Hypoglossal Nerve / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism; D009433:Neural Inhibition / Q000235:genetics; D009924:Organ Culture Techniques; D010641:Phenotype; D017729:Presynaptic Terminals / Q000378:metabolism; D013216:Reflex, Startle / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D050487:Glycine Plasma Membrane Transport Proteins; C493270:Slc6a5 protein, mouse; D005998:Glycine