Exon 2 was flanked by loxP sites and an FRT site flanked neomycin resistance gene cassette with an additional loxP site was inserted downstream in intron 2. Flp-mediated recombination removed the neo cassette. Exon 2 was deleted through cre-mediated recombination, creating a knock-out allele. In situ hybridization analysis confirmed the absence of transcript in homozygous mutant brains. Furthermore, GPR88-mediated [35S]-GTPgammaS binding was abolished in the striatum, demonstrating lack of GPR88 receptor signaling in mutant mice. (J:236208)