Mice Devoid of γ -Aminobutyrate Type A Receptor β 3 Subunit have Epilepsy, Cleft Palate, and Hypersensitive Behavior
γ -Aminobutyric acid type A receptors (GABAA-Rs) mediate the bulk of rapid inhibitory synaptic transmission in the central nervous system. The β 3 subunit is an essential component of the GABAA-R in many brain regions, especially during development, and is implicated in several pathophysiologic proc...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 8; pp. 4143 - 4148 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
National Academy of Sciences of the United States of America
15.04.1997
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Subjects | |
Online Access | Get full text |
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Summary: | γ -Aminobutyric acid type A receptors (GABAA-Rs) mediate the bulk of rapid inhibitory synaptic transmission in the central nervous system. The β 3 subunit is an essential component of the GABAA-R in many brain regions, especially during development, and is implicated in several pathophysiologic processes. We examined mice harboring a β 3 gene inactivated by gene targeting. GABAA-R density is approximately halved in brain of β 3-deficient mice, and GABAA-R function is severely impaired. Most β 3-deficient mice die as neonates; some neonatal mortality, but not all, is accompanied by cleft palate. β 3-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 β 3 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. β 3-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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.94.8.4143 |