Long-Range Interactions in Neuronal Gene Expression: Evidence from Gene Targeting in the GABAA Receptor β2–α6–α1–γ2 Subunit Gene Cluster

Abstract

Clustering of GABAA receptor α1, α6, β2, and γ2 subunit genes on mouse chromosome 11/human chromosome 5 may have functional significance for coordinating expression patterns, but until now there has been no evidence for cross-talk between the genes. However, altering the structure of the α6 gene, specifically expressed in the cerebellum, with neomycin gene insertions in two different experiments unexpectedly reduced the expression of the widespread α1 and β2 genes in the forebrain. There were corresponding reductions in the levels of α1 and β2 subunit proteins and in autoradiographic ligand binding densities to GABAA receptors in the forebrain of α6−/− mice. The γ2 mRNA level was not changed, nor were β3 and δ mRNAs. The data suggest that elements in the neo gene may have an influence over long distances in the GABAA subunit gene complex on as yet undefined structures coordinating the expression of the α1 and β2 genes.