Cloning and characterization of a novel variant of rat GABA(B)R1 with a truncated C-terminus

The gamma -aminobutyric acid B receptor (GABA(B)R) belong to the G-prorein- coupled receptor superfamily and has been identified as a mediator in the t ransmission of slow inhibitory neurotransmission in the mammalian central n ervous system. Two types of GABA(B)R have been cloned, GABA(B)R1 and R2. GA BA(B)R2 is co-expressed with GABA(B)R1 in many brain regions and inwardly r ectifying potassium channels are activated by GABA(B)R agonists only upon c o-expression of GABA,RI with GABA(B)R2. Several splice variants of GABA(B)R 1 receptors have been cloned from rat brain library. Using a rat hippocampa l cDNA library, we have isolated a novel cDNA clone of GABA, receptor conta ining an insert of 124 bp between exon 3 and exon 4. This insert occurred b etween the regions encoding the Sushi domain and leucine binding protein (L BP)-like domain. The insert and subsequent frame shift generated a cDNA tha t codes for a truncated polypeptide of 239 amino acids lacking the C-termin us. Analysis of the deduced amino acid sequence of the new cDNA clone, term ed GABA(B)R1g, showed that it was identical to the first 157 amino acids of GABA(B)R1a, but diverged thereafter. The C-terminal region of GABA(B)R1g c ontained two cysteine residues. GABA(B)R1g was expressed in both brain and peripheral tissues. Northern blot analysis demonstrated that two transcript s (4.5 kb and 4.0 kb) exist in hippocampus. in addition, studies of hippoca mpus in developing animals indicated that the expression of GABA(B)R1g is m aximal at postnatal day four. GABA(B)R1g could be generated by alternative splicing of the GABA(B)R1 gene. (C) 2001 Elsevier Science B.V. All rights r eserved.