Differential Localization of Two Alternatively Spliced GABAA Receptor gamma2-Subunit mRNAs in the Chick Brain.

Two variants of the GABAA receptor gamma2 subunit are known to exist, which differ by the presence (gamma2L) or absence (gamma2S) of eight amino acids in the presumed intracellular loop between the third and fourth membrane-spanning domains. These variants have been shown to be generated by alternative splicing of the gamma2-subunit primary gene transcript in mouse (Kofuji et al., J. Neurochem., 56, 713 - 715, 1991), and in bovine and human (Whiting et al., Proc. Natl. Acad. Sci. USA, 87, 9966 - 9970, 1990) brain. We describe here the cloning, from chick (Gallus domesticus) brain, of cDNAs that encode the gamma2L and gamma2S subunits, and report on the regional and cellular localization of the corresponding mRNAs as revealed by in situ hybridization histochemistry with transcript-specific oligonucleotide probes. While the two transcripts are found to be colocalized throughout the chick neuroaxis, certain nuclei (for example, the nucleus isthmi, pars magnocellularis, the nucleus isthmi, pars parvocellularis, the nucleus solitarius and the paleostriatum primitivum) are found to contain predominantly either the gamma2S- or the gamma2L-subunit mRNA. We conclude that receptors that contain either the gamma2S or the gamma2L subunit occur, and that these probably have functionally different roles in the modulation of neurotransmission in the central nervous system. In addition, our data indicate that certain cells may produce both transcripts. Consequently, these will have either a single receptor subtype that contains both a gamma2S and a gamma2L subunit, or two receptor subtypes, one of which contains a gamma2S subunit and the other a gamma2L subunit.