TY - JOUR
T1 - Identification, expression, and pharmacology of a cys23-ser23 substitution in the human 5-ht2c receptor gene (htr2c)
AU - Lappalainen, Jaakko
AU - Zhang, Li
AU - Dean, Michael
AU - Oz, Murat
AU - Ozaki, Norio
AU - Yu, Da hong
AU - Virkkunen, Matti
AU - Weight, Forrest
AU - Linnoila, Markku
AU - Goldman, David
PY - 1995/5/20
Y1 - 1995/5/20
N2 - The function of brain serotonin-2C (5-HT2C) receptors, including behavioral and neurochemical responses to 5-HT2C agonist challenge, has been suggested to be abnormal in individuals with neuropsychiatric disorders. Thus, it is important to identify polymorphisms and functional variants within this gene. Using SSCP analysis, we identified a Cys23-Ser23 substitution (designated 5-HT2Ccys and 5-HT2Cser) in the first hydrophobic region of the human 5-HT2C receptor. Allele frequencies in unrelated Caucasians were 0.13 and 0.87 for 5-HT2Cser and 5-HT2Ccys, respectively. DNAs from informative CEPH families were typed for this polymorphism and analyzed with respect to 20 linked markers on the X chromosome. Linkage analysis placed the 5-HT2C receptor gene (HTR2C) on Xq24. To evaluate whether this amino acid substitution causes a variant function of this receptor, recombinant human 5-HT2Ccys and 5-HT2Cser receptors were expressed in Xenopus oocytes and tested for responses to 5-HT using electrophysiological techniques. Concentration-response curves for 5-HT were not significantly different in oocytes expressing either form of the receptor, suggesting that the 5-HT2Ccys and 5-HT2Cser receptor proteins may not differ in their responses to serotonin under baseline physiological conditions.
AB - The function of brain serotonin-2C (5-HT2C) receptors, including behavioral and neurochemical responses to 5-HT2C agonist challenge, has been suggested to be abnormal in individuals with neuropsychiatric disorders. Thus, it is important to identify polymorphisms and functional variants within this gene. Using SSCP analysis, we identified a Cys23-Ser23 substitution (designated 5-HT2Ccys and 5-HT2Cser) in the first hydrophobic region of the human 5-HT2C receptor. Allele frequencies in unrelated Caucasians were 0.13 and 0.87 for 5-HT2Cser and 5-HT2Ccys, respectively. DNAs from informative CEPH families were typed for this polymorphism and analyzed with respect to 20 linked markers on the X chromosome. Linkage analysis placed the 5-HT2C receptor gene (HTR2C) on Xq24. To evaluate whether this amino acid substitution causes a variant function of this receptor, recombinant human 5-HT2Ccys and 5-HT2Cser receptors were expressed in Xenopus oocytes and tested for responses to 5-HT using electrophysiological techniques. Concentration-response curves for 5-HT were not significantly different in oocytes expressing either form of the receptor, suggesting that the 5-HT2Ccys and 5-HT2Cser receptor proteins may not differ in their responses to serotonin under baseline physiological conditions.
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U2 - 10.1006/geno.1995.1042
DO - 10.1006/geno.1995.1042
M3 - Article
C2 - 7557992
AN - SCOPUS:0029032864
SN - 0888-7543
VL - 27
SP - 274
EP - 279
JO - Genomics
JF - Genomics
IS - 2
ER -