The widespread use of gene knockout technology promotes the course of the research of gene function in post-genomic era greatly. Recently, the research of p38α knockout mice, which is one member of MAPKs, is very typical in filtering noise from critical signals in signal transduction and translating phenotype into gene function. Looking back on the research of p38α knockout mice showed: the reasonable use of gene knockout technology, based on carefully designed and analyzed mutant mice, is very important for defining the function in vivo of important signal molecular and pushing forward the research of function gene.