title: STOP knockout and NMDA NR1 hypomorphic mice exhibit deficits in sensorimotor gating.
abstract: Schizophrenia is a chronic and debilitating disease which is thought to arise from a neuro-developmental disorder. Both the stable tubule-only polypeptide (STOP) protein and the N-methyl-D-aspartate (NMDA) NR1 subunit are involved in neuronal development and physiology. It has therefore been postulated that transgenic mice lacking either the STOP or the NMDAR1 gene would show a 'schizophrenic-like' phenotype. Here, STOP knockout and NMDA NR1 hypomorphic mice were assessed in a behavioural measure that can be used to detect schizophrenic-like phenotypes: a change in sensorimotor gating, measured through prepulse inhibition (PPI). STOP knockout mice were further assessed in another measure of 'schizophrenic-like behaviour': hyperlocomotion. The PPI deficit exhibited by both the STOP knockout and NMDA knockdown mice could not be reversed by acute treatment with the atyptical antipsychotic, clozapine (1 mg/kg, i.p.) but the hyperlocomotion shown by the STOP knockout mice was reversed with the same acute dose of clozapine.
authors.affiliation: Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK. rosa_fradley@merck.com
authors.forename: Rosa L
authors.initials: RL
authors.lastname: Fradley
authors.forename: Gillian F
authors.initials: GF
authors.lastname: O'Meara
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Newman
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.forename: Didier
authors.initials: D
authors.lastname: Job
authors.forename: David S
authors.initials: DS
authors.lastname: Reynolds
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003024:Clozapine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency*; D012022:Reflex, Acoustic / Q000187:drug effects / Q000235:genetics; D045442:Rotarod Performance Test / Q000379:methods; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology*; D013550:Swimming; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine; D003024:Clozapine