title: Genetic analysis of specific and redundant roles for p38alpha and p38beta MAPKs during mouse development.
abstract: 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.
authors.affiliation: Centro Nacional de Investigaciones Oncológicas, 28019 Madrid, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: del Barco Barrantes
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Coya
authors.forename: Flavio
authors.initials: F
authors.lastname: Maina
authors.forename: J Simon C
authors.initials: JS
authors.lastname: Arthur
authors.forename: Angel R
authors.initials: AR
authors.lastname: Nebreda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048290:Mitogen-Activated Protein Kinase 11 / Q000235:genetics* / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14