PMID: 7644489Aug 15, 1995

Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors

Proceedings of the National Academy of Sciences of the United States of America
U GüntherB Lüscher

Abstract

Vigilance, anxiety, epileptic activity, and muscle tone can be modulated by drugs acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABAA) receptors. In vivo, BZ sites are potential targets for endogenous ligands regulating the corresponding central nervous system states. To assess the physiological relevance of BZ sites, mice were generated containing GABAA receptors devoid of BZ sites. Following targeted disruption of the gamma 2 subunit gene, 94% of the BZ sites were absent in brain of neonatal mice, while the number of GABA sites was only slightly reduced. Except for the gamma 2 subunit, the level of expression and the regional and cellular distribution of the major GABAA receptor subunits were unaltered. The single channel main conductance level and the Hill coefficient were reduced to values consistent with recombinant GABAA receptors composed of alpha and beta subunits. The GABA response was potentiated by pentobarbital but not by flunitrazepam. Diazepam was inactive behaviorally. Thus, the gamma 2 subunit is dispensable for the assembly of functional GABAA receptors but is required for normal channel conductance and the formation of BZ sites in vivo. BZ sites are not essential for embryonic devel...Continue Reading

References

Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·A Buhr, E Sigel
Jan 23, 1999·Journal of Neurophysiology·G J StreckerF E Dudek
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·R M MihalekGregg E Homanics
Jun 16, 1999·British Journal of Pharmacology·A DemuroR Miledi
Jun 8, 2001·Alcoholism, Clinical and Experimental Research·S UenoM P Mascia
Dec 14, 2001·Behavioural Pharmacology·B OlivierM Toth
Dec 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rachel JurdUwe Rudolph
May 31, 2013·Annals of Neurology·Jing-Qiong KangRobert L Macdonald
Mar 13, 2013·Critical Care Medicine·Robert D SandersTracy Hussell
Oct 29, 2013·Annual Review of Pharmacology and Toxicology·Uwe Rudolph, H Mohler
May 26, 2015·Nature Neuroscience·Jing-Qiong KangRobert L Macdonald
Aug 22, 2017·International Journal of Molecular Sciences·Karan GovindpaniAndrea Kwakowsky
Sep 14, 2017·Developmental Neurobiology·Joshua M Lorenz-Guertin, Tija C Jacob
May 18, 2018·Journal of Neuroendocrinology·A M Iturra-MenaA Dagnino-Subiabre
Oct 28, 1998·Physiological Reviews·M R Picciotto, K Wickman
Feb 1, 1996·Molecular Neurobiology·Angel L De Blas
Apr 11, 2003·Neurogenetics·Deborah A FinnJohn C Crabbe
Aug 17, 2004·Epilepsy Currents·C Guin-Ting Wong, O Carter Snead
May 23, 2002·Brain : a Journal of Neurology·Dimitri M Kullmann
Mar 28, 2002·Physiological Reviews·Thomas J JentschAnselm A Zdebik
Oct 7, 2003·Annual Review of Neuroscience·Jeffrey L Noebels
Oct 7, 2006·The Journal of Physiology·Martin Mortensen, Trevor G Smart
Apr 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Claude M SchofieldJohn R Huguenard

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GNG2 gene
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