Pharmacogenomics of thyroid disease in molecular target discovery

我们已经确定了一种新的人类环核苷酸磷酸二酯酶（PDE）同工酶，我们指定为PDE 8B 1。北方印迹分析表明，编码PDE 8B的mRNA在甲状腺中特异性地表达，而PDE 8A在各种组织中广泛表达。此外，我们已经表征了人PDE 8B的基因，并克隆了两个剪接变体（PDE 8B 2和PDE 8B 3）。PDE 8B基因定位于5号染色体长臂（5 q13），由22个外显子组成，跨越200 kb。PDE 8B 2和PDE 8B 3都在PAS结构域中具有缺失。RT-PCR分析显示，虽然PDE 8B 1是甲状腺中最丰富的变体，但PDE 8B 3，而不是PDE 8B 1，是大脑中最丰富的变体。这些发现表明，外显子的选择性使用产生三种不同的PDE 8B变体，其表现出组织特异性表达模式。

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.