Conservation of the hydroxysteroid sulfotransferase SULT2B1 gene structure in the mouse: pre- and postnatal expression, kinetic analysis of isoforms, and comparison with prototypical SULT2A1.
Conservation of the hydroxysteroid sulfotransferase SULT2B1 gene structure in the mouse: pre- and postnatal expression, kinetic analysis of isoforms, and comparison with prototypical SULT2A1.
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DOI：
10.1210/en.2002-221011
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发表时间：
2003-04
期刊：
影响因子：
4.8
通讯作者：
C. Shimizu;H. Fuda;H. Yanai;C. Strott
中科院分区：
文献类型：
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作者：
C. Shimizu;H. Fuda;H. Yanai;C. Strott
一种新的小鼠羟类固醇磺基转移酶cDNA已被克隆，其基因结构的组织已被确定。新的小鼠磺基转移酶SULT 2B 1a及其密切相关的同种型SULT 2B 1b源自单一SULT 2B 1基因，作为选择性外显子I和差异剪接的结果。因此，两种SULT 2B 1亚型之间的唯一结构区别在于其氨基末端。重要的是，与原型小鼠羟基类固醇磺基转移酶SULT 2A 1相反，SULT 2B 1亚型对胆固醇具有偏好。实时RT-PCR显示，SULT 2B 1a亚型在脑和脊髓中表达最丰富，而SULT 2B 1b和SULT 2A 1在中枢神经系统中表达较弱。另一方面，SULT 2B 1b同种型是皮肤中表达的最突出的羟基类固醇磺基转移酶，而SULT 2A 1在肝脏中显著表达。三种SULT 2同工酶的底物特异性和差异表达模式强烈表明它们具有不同的生物学作用。进一步感兴趣的是，小鼠SULT 2B 1和SULT 2A 1基因在胚胎发育期间差异表达，前者在E8.5-E19的所有阶段表达，而后者直到E19才表达。据推测，在胚胎发育期间，SULT 2B 1b是正常皮肤发育所必需的硫酸胆固醇的产生所必需的，而SULT 2B 1a产生硫酸双烯醇酮，这是中枢神经系统发育期间必需的神经类固醇。
A novel mouse hydroxysteroid sulfotransferase cDNA has been cloned, and organization of its gene structure has been determined. The new mouse sulfotransferase, SULT2B1a, and its closely related isoform, SULT2B1b, are derived from a single SULT2B1 gene as a result of an alternative exon I and differential splicing. Thus, the only structural distinction between the two SULT2B1 isoforms is at their amino-terminal ends. Importantly, in contrast to the prototypical mouse hydroxysteroid sulfotransferase SULT2A1, the SULT2B1 isoforms have a predilection for cholesterol. Real-time RT-PCR reveals that the SULT2B1a isoform is most abundantly expressed in the brain and spinal cord, whereas SULT2B1b and SULT2A1 are weakly, if at all, expressed in the central nervous system. On the other hand, the SULT2B1b isoform is the most prominent hydroxysteroid sulfotransferase expressed in skin, whereas SULT2A1 is strikingly expressed in the liver. The substrate specificities and differential expression patterns of the three SULT2 isozymes strongly suggest that they have distinct biologic roles to play. Of further interest, the mouse SULT2B1 and SULT2A1 genes are differentially expressed during embryonic development, with the former being expressed at all stages from E8.5-E19, whereas the latter is not expressed until E19. It is speculated that, during embryonic development, SULT2B1b is required for production of cholesterol sulfate essential for normal skin development, whereas SULT2B1a produces pregnenolone sulfate, an essential neurosteroid during development of the central nervous system.