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

• DOI: 10.1073/pnas.92.17.7749
• Publication Date: 2006-05-31T13:17:17Z
• Authors: U Günther; J Benson; D Benke; J M Fritschy; G Reyes; F Knoflach; F Crestani; A Aguzzi; M Arigoni; Y Lang; H Bluethmann; H Mohler; B Lüscher
• Keywords: GABAA-rho receptor; Gamma-Aminobutyric Acid; Flunitrazepam; Flumazenil; Cys-loop receptors; Gamma subunit

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 corresponding central nervous system states. To assess physiological relevance sites, mice were generated containing GABAA receptors devoid sites. Following targeted disruption gamma 2 subunit gene, 94% absent in brain neonatal mice, while number GABA was only slightly reduced. Except subunit, level expression regional cellular distribution major receptor subunits unaltered. The single channel main conductance Hill coefficient reduced to values consistent with recombinant composed alpha beta subunits. response potentiated pentobarbital but not flunitrazepam. Diazepam inactive behaviorally. Thus, is dispensable assembly functional required normal formation vivo. essential embryonic development, as suggested body weight histology newborn mice. Postnatally, however, function associated retarded growth, sensorimotor dysfunction, drastically life-span. lack postnatal regulation might contribute this phenotype.