Disease-Specific Human Glycine Receptor α1 Subunit Causes Hyperekplexia Phenotype and Impaired Glycine- and GABAA-Receptor Transmission in Transgenic Mice

Journal of Neuroscience

Volumn 22, Issue 7, 2002, Pages 2505-2512

  Becker, Lore ^a,b   Von Wegerer, Jörg ^c   Schenkel, Johannes ^b   Zeilhofer, Hanns Ulrich ^d   Swandulla, Dieter ^c   Weiher, Hans ^a  

^a INSTITUT FÜR DIABETESFORSCHUNG   (Germany)

^b KARLSRUHE INSTITUTE OF TECHNOLOGY   (Germany)

^c UNIVERSITY OF BONN   (Germany)

^d UNIVERSITY HOSPITAL ERLANGEN   (Germany)

Author keywords

GABAA receptor; Glycine receptor; Hyperekplexia; Impaired postsynaptic inhibition; Neuromotor phenotype; Transgenic mouse model

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ALPHA1 GLYCINE RECEPTOR; GLYCINE RECEPTOR; RECEPTOR SUBUNIT; UNCLASSIFIED DRUG; GLYCINE; GLYCINE RECEPTOR ALPHA1; LIGAND; PROTEIN SUBUNIT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; ELECTROPHYSIOLOGY; FEMALE; GENE EXPRESSION; GENE MUTATION; MALE; MOUSE; NONHUMAN; POSTSYNAPTIC INHIBITION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION; SPINAL CORD VENTRAL HORN; STARTLE EPILEPSY; TRANSGENIC MOUSE; WILD TYPE; ANIMAL; AUTORADIOGRAPHY; BRAIN; DISEASE MODEL; DOMINANT GENE; GENETICS; HUMAN; IN VITRO STUDY; METABOLISM; MUTATION; MYOCLONUS; NERVE CELL INHIBITION; NEUROMUSCULAR DISEASE; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PHYSIOLOGY; SPINAL CORD; STARTLE REFLEX; SYNAPTIC TRANSMISSION; TREMOR;

ANIMALS; AUTORADIOGRAPHY; BRAIN; DISEASE MODELS, ANIMAL; FEMALE; GENES, DOMINANT; GLYCINE; HUMANS; LIGANDS; MALE; MICE; MICE, TRANSGENIC; MUTATION; MYOCLONUS; NEURAL INHIBITION; NEUROMUSCULAR DISEASES; PHENOTYPE; PROTEIN SUBUNITS; RECEPTORS, GABA-A; RECEPTORS, GLYCINE; SPINAL CORD; STARTLE REACTION; SYNAPTIC TRANSMISSION; TREMOR;

EID: 0036548542     PISSN: 02706474     EISSN: None     Source Type: Journal    
DOI: 10.1523/jneurosci.22-07-02505.2002     Document Type: Article

References (39)

1. Andrew M, Owen MJ (1997) Hyperekplexia: abnormal startle response due to glycine receptor mutations. Br J Psychiatry 170:106-108.
2. Becker CM, Hermans-Borgmeyer I, Schmitt B, Betz H (1986) The glycine receptor deficiency of the mutant mouse spastic: evidence for normal glycine receptor structure and localization. J Neurosci 6:1358-1364.
3. Becker CM, Schmieden V, Tarroni P, Strasser U, Betz H (1992) Isoform-selective deficit of glycine receptors in the mouse mutant spastic. Neuron 8:283-289.
4. Becker L, Hartenstein B, Schenkel J, Kuhse J, Betz H, Weiher H (2000) Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor β-subunit: an animal model of startle disease. Eur J Neurosci 12:27-32.
5. Bekkers JM, Stevens CF (1989) NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus. Nature 341:230-233
6. Betz H (1992) Structure and function of inhibitory glycine receptors. Q Rev Biophys 25:381-394.
7. A-receptors at GABAergic synaptic contacts demonstrated by triple immunofluorescence staining. Brain Res 642:59-69.
8. 1) results in progressive neurological symptoms and juvenile death. Hum Mol Genet 3:2025-2030.
9. Burger PM, Hell J, Mehl E, Krasel C, Lottspeich F, Jahn R (1991) GABA and glycine in synaptic vesicles: storage and transport characteristics. Neuron 7:287-293.
10. Butler MH, Hayashi A, Ohkoshi N, Villmann C, Becker CM, Feng G, De Camilli P, Solimena M (2000) Autoimmunity to gephyrin in stiff-man syndrome. Neuron 26:307-312.
11. Chen Q, Moulder K, Tenkova T, Hardy K, Olney JW, Romano C (1999) Excitotoxic cell death dependent on inhibitory receptor activation. Exp Neurol 160:215-225.
12. Dodt HU, Zieglgansberger W (1994) Infrared videomicroscopy: a new look at neuronal structure and function. Trends Neurosci 17:453-458.
13. Dumoulin A, Rostaing P, Bedet C, Lévi S, Isambert M-F, Henry J-P, Triller A, Gasnier B (1999) Presence of the vesicular inhibitory amino acid transporter in GABAergic and glycinergic synaptical terminal boutons. J Cell Sci 112:811-823.
14. 2 subunit and gephyrin. Nat Neurosci 1:563-571.
15. Feng G, Tintrup H, Kirsch J, Nichol MC, Kuhse J, Betz H, Sanes JR (1998) Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity. Science 282:1321-1324.
16. Floeter MK, Andermann F, Andermann E, Nigro M, Hallett M (1996) Physiological studies of spinal inhibitory pathways in patients with hereditary hyperekplexia. Neurology 46:766-772.
17. Grenningloh G, Pribilla I, Prior P, Multhaup G, Beyreuther K, Taleb O, Betz H (1990a) Cloning and expression of the 58 kd β subunit of the inhibitory glycine receptor. Neuron 4:963-970.
18. Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker CM, Betz H (1990b) Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J 9:771-776.
19. Hartenstein B, Schenkel J, Kuhse J, Besenbeck B, Kling C, Becker CM, Betz H, Weiher H (1996) Low level expression of glycine receptor β subunit transgene is sufficient for phenotype correction in spastic mice. EMBO J 15:1275-1282.
20. Jonas P, Bischofberger J, Sandkuhler J (1998) Corelease of two fast neurotransmitters at a central synapse. Science 281:419-424.
21. Kingsmore SF, Giros B, Suh D, Bieniarz M, Caron MG, Seldin MF (1994) Glycine receptor β-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet 7:136-141.
22. A receptor clustering in gephyrin-deficient mice. J Neurosci 19:9289-9297.
23. Langosch D, Laube B, Rundstöm N, Schmieden V, Bormann J, Betz H (1994) Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J 2013:4223-4228.
24. Laube B, Langosch D, Betz H, Schmieden V (1995) Hyperekplexia mutations of the glycine receptor unmask the inhibitory subsite for β-amino-acids. NeuroReport 6:897-900.
25. Malinow R, Tsien RW (1990) Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices. Nature 346:177-180.
26. Malosio ML, Marqueze-Pouey B, Kuhse J, Betz H (1991) Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J 10:2401-2409.
27. Matsumoto J, Fuhr P, Nigro M, Hallett M (1992) Physiological abnormalities in hereditary hyperekplexia. Ann Neurol 32:41-50.
28. Meyer G, Kirsch J, Betz H, Langosch D (1995) Identification of a gephyrin binding motif on the glycine receptor β subunit. Neuron 15:563-572.
29. Moechars D, Lorent K, De Strooper B, Dewachter I, Van Leuven F (1996) Expression in brain of amyloid precursor protein mutated in the α-secretase site causes disturbed behavior, neuronal degeneration and premature death in transgenic mice. EMBO J 15:1265-1274.
30. Mulhardt C, Fischer M, Gass P, Simon-Chazottes D, Guenet JL, Kuhse J, Betz H, Becker CM (1994) The spastic mouse: aberrant splicing of glycine receptor β subunit mRNA caused by intronic insertion of L1 element. Neuron 13:1003-1015.
31. Rajendra S, Lynch JW, Pierce KD, French CR, Barry PH, Schofield PR (1994) Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor. J Biol Chem 269:18739-18742.
32. Ryan SG, Sherman SL, Terry JC, Sparkes RS, Torres MC, Mackey RW (1992) Startle disease, or hyperekplexia: response to clonazepam and assignment of the gene (STHE) to chromosome 5q by linkage analysis. Ann Neurol 31:663-668.
33. 1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Nat Genet 7:131-135.
34. Sagné C, El Mestikawy S, Isambert M-F, Hamon M, Henry J-P, Giros B, Gasnier B (1997) Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases. FEBS Lett 417:177-183.
35. 1 subunit in the spasmodic mouse affects agonist responses. FEBS Lett 350:71-76.
36. 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet 5:351-358.
37. Stayer C, Meinck HM (1998) Stiff-man syndrome: an overview. Neurologia 13:83-88.
38. Suhren O, Bruyn GW, Tuynman JA (1966) Hyperekplexia: a hereditary syndrome. J Neurol Sci 3:577-605.
39. White WF, Heller AH (1982) Glycine receptor alteration in the mutant mouse spastic. Nature 298:655-657.