GABAAReceptor ε and θ Subunits Display Unusual Structural Variation between Species and Are Enriched in the Rat Locus Ceruleus

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Abstract
Previously, GABAA receptor ε and θ subunits have been identified only in human. Here, we describe properties of the ε and θ subunit genes from mouse and rat that reveal an unusually high level of divergence from their human homologs. In addition to a low level of amino acid sequence conservation (∼70%), the rodent ε subunit cDNAs encode a unique Pro/Glx motif of ∼400 residues within the N-terminal extracellular domain of the subunits. Transcripts of the rat ε subunit were detected in brain and heart, whereas the mouse θ subunit mRNA was detectable in brain, lung, and spleen by Northern blot analysis. In situ hybridization revealed a particularly strong signal for both subunit mRNAs in rat locus ceruleus in which expression was detectable from the first postnatal day. Lower levels of coexpression were also detected in other brainstem nuclei and in the hypothalamus. However, the expression pattern of θ subunit mRNA was more widespread than that of ε subunit, being found also in the cerebral cortex of rat pups. In contrast to primate brain, neither subunit was expressed in the hippocampus or substantia nigra. The results indicate that GABAA receptor ε and θ subunits are evolving at a much faster rate than other known GABAAreceptor subunits and that their expression patterns and functional properties may differ significantly between species.