GABA A receptor changes in δ subunit‐deficient mice: Altered expression of α4 and γ2 subunits in the forebrain

The δ subunit is a novel subunit of the pentameric γ‐aminobutyric acid (GABA) A receptor that conveys special pharmacological and functional properties to recombinant receptors and may be particularly important in mediating tonic inhibition. Mice that lack the δ subunit have been produced by gene‐targeting technology, and these mice were studied with immunohistochemical and immunoblot methods to determine whether changes in GABA A receptors were limited to deletion of the δ subunit or whether alterations in other GABA A receptor subunits were also present in the δ subunit knockout (δ–/–) mice. Immunohistochemical studies of wild‐type mice confirmed the restricted distribution of the δ subunit in the forebrain. Regions with moderate to high levels of δ subunit expression included thalamic relay nuclei, caudate‐putamen, molecular layer of the dentate gyrus, and outer layers of the cerebral cortex. Virtually no δ subunit labeling was evident in adjacent regions, such as the thalamic reticular nucleus, hypothalamus, and globus pallidus. Comparisons of the expression of other subunits in δ–/– and wild‐type mice demonstrated substantial changes in the α4 and γ2 subunits of the GABA A receptor in the δ–/– mice. γ2 Subunit expression was increased, whereas α4 subunit expression was decreased in δ–/– mice. Importantly, alterations of both the α4 and the γ2 subunits were confined primarily to brain regions that normally expressed the δ subunit. This suggests that the additional subunit changes are directly linked to loss of the δ subunit and could reflect local changes in subunit composition and function of GABA A receptors in δ–/– mice. J. Comp. Neurol. 446:179–197, 2002. © 2002 Wiley‐Liss, Inc.