Project Summary

Xianjih Zhou, Ph.D. (Young Investigator 2005) of the University of California at San Diego, plans to study variants in the gene for GRK3, which has been strongly associated with bipolar disorder. GRK3 sequence analysis has revealed a significant link to the disease of two SNPs, or variants, in the GRK3 proximal promoter, a region that regulates the expression of the gene. Interestingly, one SNP disrupts a Spl consensus binding sequence—involved in gene regulation—while the other lies at the base of a potential hairpin structure in the 5’ untranslated region of the GRK3 gene. Spl binding site disruption has been reported in the promoter of several candidate genes for schizophrenia. Also, recent studies by Dr. Zhou have demonstrated that reduced expression of Sp4 gene, a Spl family member, caused robust sensorimotor gating deficiency in mice. These findings therefore warrant further functional studies of the SNPs, particularly the one in the Spl binding site, in the regulation of human GRK3 expression, which is what Dr. Zhou is proposing.

Program Area: MOOD DISORDERS\Bipolar

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