{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:43:27Z","timestamp":1792734207983,"version":"4.5.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,4,15]]},"abstract":"<jats:p>\n                    \u03b3-Aminobutyric acid type A receptors (GABA\n                    <jats:sub>A<\/jats:sub>\n                    -Rs) mediate the bulk of rapid inhibitory synaptic transmission in the central nervous system. The \u03b23 subunit is an essential component of the GABA\n                    <jats:sub>A<\/jats:sub>\n                    -R in many brain regions, especially during development, and is implicated in several pathophysiologic processes. We examined mice harboring a \u03b23 gene inactivated by gene targeting. GABA\n                    <jats:sub>A<\/jats:sub>\n                    -R density is approximately halved in brain of \u03b23-deficient mice, and GABA\n                    <jats:sub>A<\/jats:sub>\n                    -R function is severely impaired. Most \u03b23-deficient mice die as neonates; some neonatal mortality, but not all, is accompanied by cleft palate. \u03b23-deficient mice that survive are runted until weaning but achieve normal body size by adulthood, although with reduced life span. These mice are fertile but mothers fail to nurture offspring. Brain morphology is grossly normal, but a number of behaviors are abnormal, consistent with the widespread location of the \u03b23 subunit. The mice are very hyperactive and hyperresponsive to human contact and other sensory stimuli, and often run continuously in tight circles. When held by the tail, they hold all paws in like a ball, which is frequently a sign of neurological impairment. They have difficulty swimming, walking on grids, and fall off platforms and rotarods, although they do not have a jerky gait. \u03b23-deficient mice display frequent myoclonus and occasional epileptic seizures, documented by electroencephalographic recording. Hyperactivity, lack of coordination, and seizures are consistent with reduced presynaptic inhibition in spinal cord and impaired inhibition in higher cortical centers and\/or pleiotropic developmental defects.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.8.4143","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"4143-4148","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":397,"title":["Mice devoid of \u03b3-aminobutyrate type A receptor \u03b23 subunit have epilepsy, cleft palate, and hypersensitive\u2009behavior"],"prefix":"10.1073","volume":"94","author":[{"given":"Gregg E.","family":"Homanics","sequence":"first","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"DeLorey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard L.","family":"Firestone","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Handforth","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil L.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Krasowski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E. M.","family":"Rick","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa R.","family":"Korpi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka","family":"M\u00e4kel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray H.","family":"Brilliant","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuko","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology\/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095; Neurology Service, West Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073; Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637; Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland;..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,4,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3100001"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)80023-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-11-04151.1992"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-03-01040.1992"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/364448a0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-344"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2815"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-0348-8990-2_30"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(95)80209-5"},{"key":"e_1_3_3_10_2","first-page":"330","volume":"49","author":"Wagstaff J","year":"1991","unstructured":"J Wagstaff, J H M Knoll, J Fleming, E F Kirkness, A Martin-Gallardo, F, J M Greenberg, J Grahm, J Menninger, D Ward, J C Venter, M Lalande Am J Hum Genet 49, 330\u2013337 (1991).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_11_2","unstructured":"Minassian B. 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