Reduced Body Weight and Increased Postimplantation Fetal Death in Tyrosylprotein Sulfotransferase-1-deficient Mice*
Reduced Body Weight and Increased Postimplantation Fetal Death in Tyrosylprotein Sulfotransferase-1-deficient Mice*
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DOI：
10.1074/jbc.m202420200
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发表时间：
2002-06
期刊：
影响因子：
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通讯作者：
Y. Ouyang;J. Crawley;C. Aston;K. Moore
中科院分区：
文献类型：
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作者：
Y. Ouyang;J. Crawley;C. Aston;K. Moore
酪氨酸硫酸化是由两种高尔基同工酶之一介导的，称为酪氨酸蛋白硫转移酶（TPST-1和TPST-2）。已知相对少量的蛋白质会经历酪氨酸硫酸化，包括某些粘附分子、g蛋白偶联受体、凝血因子、蛇形蛋白、细胞外基质蛋白和激素。作为探索这些酶在体内的作用以及它们如何在生物系统中相互作用的一种方法，我们通过靶向破坏Tpst1基因产生了tpst -1缺陷小鼠。Tpst1 +/−小鼠外观正常，杂交后产仔大小正常，具有孟德尔遗传分布和性别均匀分布。Tpst1−/−小鼠看起来很健康，但平均体重比Tpst1 +/+对照组低约5%。此外，我们发现虽然Tpst1−/−雄性和雌性的生育能力正常，但Tpst1−/−雌性的产仔数量明显较少，因为在交媾后8.5至15.5天之间胎儿死亡。这些发现表明，有一些蛋白质参与调节体重和生殖生理，这些蛋白质需要酪氨酸硫酸化才能达到最佳功能，但尚未得到描述。我们的研究结果也有力地支持了TPST-1和TPST-2具有不同的生物学作用的结论，这可能反映了它们在大分子底物特异性上的差异。
Tyrosine sulfation is mediated by one of two Golgi isoenzymes, called tyrosylprotein sulfotransferases (TPST-1 and TPST-2). A relatively small number of proteins are known to undergo tyrosine sulfation, including certain adhesion molecules, G-protein-coupled receptors, coagulation factors, serpins, extracellular matrix proteins, and hormones. As one approach to explore the role of these enzymes in vivo and how they might interact in biological systems, we have generated TPST-1-deficient mice by targeted disruption of the Tpst1 gene.Tpst1 +/− mice appear normal and, when interbred, yield litters of normal size with a Mendelian genetic distribution and an equal sex distribution.Tpst1 −/− mice appear healthy but have ≈5% lower average body weight than Tpst1 +/+controls. In addition, we show that although fertility ofTpst1 −/− males and females per seis normal, Tpst1 −/− females have significantly smaller litters because of fetal death between 8.5 and 15.5 days postcoitum. These findings suggest that there are proteins involved in regulation of body weight and reproductive physiology, which require tyrosine sulfation for optimal function that are yet to be described. Our findings also strongly support the conclusion that TPST-1 and TPST-2 have distinct biological roles that may reflect differences in their macromolecular substrate specificity.