PROPOSED SCHIZOPHRENIA-RELATED GENE POLYMORPHISM - EXPRESSION OF THE SER9GLY MUTANT HUMAN DOPAMINE D-3 RECEPTOR WITH THE SEMLIKI-FOREST-VIRUS SYSTEM

Homozygotes for a BalI polymorphism resulting in the Ser9Gly mutation in the human dopamine D-3 receptor gene are suggested to display a two fold higher risk of schizophrenia. The cDNAs for this mutant and the w ildtype receptor were introduced into the pSFV1C vector and recombinan t Semliki Forest virus particles generated. CHO cells infected with SF V-D-3 virus resulted in high level expression of recombinant receptor. Double infections with wildtype and Ser9Gly dopamine D-3 SFV stocks g enerated an artificial heterozygote in CHO cells. Receptor binding ana lysis of several structurally different dopamine D-3 ligands showed si milar pharmacological properties for all compounds tested except for d opamine and the D-3-selective ligand GR99841. A significantly higher d opamine binding afffinity for the Ser9Gly homozygote was detected. The heterozygote binding did not differ from the wildtype. However, both the homo- and heterozygote for Ser9Gly showed significantly higher bin ding activity for GR99841 compared to the D-3 wildtype. (C) 1996 Acade mic Press, Inc.