Comparative analysis of brain proteins from p53 ‐deficient mice by two‐dimensional electrophoresis

p53 is a tumor suppressor protein that regulates many cellular processes including the cell cycle, DNA repair, and apoptosis. It also serves as a critical regulator of neuronal apoptosis in the central nervous system (CNS). To elucidate the role of p53 in the CNS, brain proteins of p53 knock‐out mice ( p53 −/−) were analyzed by two‐dimensional gel electrophoresis (2‐DE) and compared with those from p53 wild type ( p53 +/+) mice. Six types of brain tissue (temporal cortex, cerebellum, hippocampus, striatum, olfactory bulb, and cervical spinal cord) and other control tissues (lung and blood) from 18‐week‐old non‐stress‐induced mice were analyzed. The morphology of brains from p53 −/− mice appeared to be normal and identical to that of p53 +/+ mice, although lungs showed diffuse tumors that may have been caused by p53 deficiency. Comparative 2‐D gel analysis showed that, on average, 7 of 886 spots from brain tissue were p53 −/− specific, whereas 12 of 1008 spots from lung tissue were p53 −/− specific. N ‐terminal amino acid sequence was determined for p53 −/− specific proteins. In all brain tissues from p53 −/− mice, a newly identified mouse mitochondrial NADH‐ubiquinone oxidoreductase 24 kDa subunit showed decreased expression, and apolipoprotein A1 acidic forms showed increased expression. In addition, brain‐type creatine kinase B chain and tubulin β‐5 N ‐terminal fragment were increased in the p53 −/− cerebellum, and a new protein in mouse, hydroxyacylglutathione hydrolase (glyoxalase II) was decreased in the temporal cortex of p53 −/− mice. The alterations in protein expression identified in this study may imply a p53 ‐related brain function. This is the first proteomic analysis on the p53 −/− mouse brain, and further information based on this study will provide new insights into the p53 function in the CNS.