Pharmacogenomics of thyroid disease in molecular target discovery

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We have identified a novel human isozyme of cyclic nucleotide phosphodiesterase (PDE), which we designated PDE8B1. Northern blot analysis indicated that the mRNA encoding PDE8B is expressed specifically and abundantly in thyroid gland, in contrast to the wide expression of PDE8A in various tissues. Moreover, we have characterized the gene for human PDE8B and cloned two splice variants (PDE8B2 and PDE8B3). The PDE8B gene is mapped to the long arm of chromosome 5(5ql3) and is composed of 22 exons spanning over 200 kb. PDE8B2 and PDE8B3 both have deletion in the PAS domain. RT-PCR analysis revealed that while PDE8B1 is the most abundant variant in thyroid gland, PDE8B3, but not PDE8B1, is the most abundant from in brain. These finding suggest that selective usage of exons produces three different PDE8B variants that exhibit a tissue-specific expression pattern.