Centro Nacional de Investigaciones Oncológicas, 28019 Madrid, Spain.
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12764-9. doi: 10.1073/pnas.1015013108. Epub 2011 Jul 18.
p38α MAPK is an important regulator of cellular responses induced by external cues, but the elucidation of physiological functions for p38α has been complicated by the possible functional redundancy in vivo with the related family member p38β. We found that mice with combined deletion of p38α and p38β display diverse developmental defects at midgestation, including major cardiovascular abnormalities, which are observed neither in single knockout nor in double heterozygous embryos. Expression analysis indicates specific functions of p38α and p38β in the regulation of cardiac gene expression during development. By using knock-in animals that express p38β under control of the endogenous p38α promoter, we also found that p38β cannot perform all of the functions of p38α during embryogenesis. Our results identify essential roles for p38α and p38β during development and suggest that some specific functions may be explained by differences in expression patterns.
p38α MAPK 是细胞对外界刺激产生反应的重要调节因子，但由于相关家族成员 p38β 在体内可能具有功能冗余性，因此阐明 p38α 的生理功能变得复杂。我们发现，p38α 和 p38β 双重敲除的小鼠在中期妊娠时表现出多种发育缺陷，包括主要的心血管异常，而在单敲除或双杂合子胚胎中均未观察到这些缺陷。表达分析表明，p38α 和 p38β 在发育过程中对心脏基因表达的调节具有特异性功能。通过使用在内源 p38α 启动子控制下表达 p38β 的基因敲入动物，我们还发现 p38β 在胚胎发生过程中不能执行 p38α 的所有功能。我们的结果确定了 p38α 和 p38β 在发育过程中的重要作用，并表明一些特定功能可能可以通过表达模式的差异来解释。
