Genetic analysis of specific and redundant roles for p38α and p38β MAPKs during mouse development

p38 alpha MAPK is an important regulator of cellular responses induced by external cues, but the elucidation of physiological functions for p38 alpha has been complicated by the possible functional redundancy in vivo with the related family member p38 beta. We found that mice with combined deletion of p38 alpha and p38 beta 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 p38 alpha and p38 beta in the regulation of cardiac gene expression during development. By using knock-in animals that express p38 beta under control of the endogenous p38 alpha promoter, we also found that p38 beta cannot perform all of the functions of p38 alpha during embryogenesis. Our results identify essential roles for p38 alpha and p38 beta during development and suggest that some specific functions may be explained by differences in expression patterns.