PT - JOURNAL ARTICLE AU - Cyrille Sur AU - Keith A. Wafford AU - David S. Reynolds AU - Karen L. Hadingham AU - Frances Bromidge AU - Alison Macaulay AU - Neil Collinson AU - Gillian O'Meara AU - Owain Howell AU - Richard Newman AU - Janice Myers AU - John R. Atack AU - Gerard R. Dawson AU - Ruth M. McKernan AU - Paul J. Whiting AU - Thomas W. Rosahl TI - Loss of the Major GABA<sub>A</sub> Receptor Subtype in the Brain Is Not Lethal in Mice AID - 10.1523/JNEUROSCI.21-10-03409.2001 DP - 2001 May 15 TA - The Journal of Neuroscience PG - 3409--3418 VI - 21 IP - 10 4099 - http://www.jneurosci.org/content/21/10/3409.short 4100 - http://www.jneurosci.org/content/21/10/3409.full SO - J. Neurosci.2001 May 15; 21 AB - The α1β2γ2 is the most abundant subtype of the GABAA receptor and is localized in many regions of the brain. To gain more insight into the role of this receptor subtype in the modulation of inhibitory neurotransmission, we generated mice lacking either the α1 or β2 subunit. In agreement with the reported abundance of this subtype, &gt;50% of total GABAA receptors are lost in both α1−/− and β2−/− mice. Surprisingly, homozygotes of both mouse lines are viable, fertile, and show no spontaneous seizures. Initially half of the α1−/− mice died prenatally or perinatally, but they exhibited a lower mortality rate in subsequent generations, suggesting some phenotypic drift and adaptive changes. Both adult α1−/− and β2−/− mice demonstrate normal performances on the rotarod, but β2−/− mice displayed increased locomotor activity. Purkinje cells of the cerebellum primarily express α1β2γ2 receptors, and in electrophysiological recordings from α1−/− mice GABA currents in these neurons are dramatically reduced, and residual currents have a benzodiazepine pharmacology characteristic of α2- or α3-containing receptors. In contrast, the cerebellar Purkinje neurons from β2−/− mice have only a relatively small reduction of GABA currents. In β2−/− mice expression levels of all six α subunits are reduced by ∼50%, suggesting that the β2 subunit can coassemble with α subunits other than just α1. Our data confirm that α1β2γ2 is the major GABAA receptor subtype in the murine brain and demonstrate that, surprisingly, the loss of this receptor subtype is not lethal.