Altered expression of hypothetical proteins in hippocampus of transgenic mice overexpressing human Cu/Zn-superoxide dismutase 1

BACKGROUND: Cu/Zn-superoxide dismutase 1 (SOD1), encoded on chromosome 21, is a key enzyme in the metabolism of reactive oxygen species (ROS) and pathogenetically relevant for several disease states including Down syndrome (DS; trisomy 21). Systematically studying protein expression in human brain and animal models of DS we decided to carry out "protein hunting" for hypothetical proteins, i.e. proteins that have been predicted based upon nucleic sequences only, in a transgenic mouse model overexpressing human SOD1. RESULTS: We applied a proteomics approach using two-dimensional electrophoresis (2-DE) with in-gel digestion of spots followed by mass spectrometric (matrix-assisted laser desorption/ionization-time of flight) identification and quantification of hypothetical proteins using specific software. Hippocampi of wild type, hemizygous and homozygous SOD1 transgenic mice (SOD1-TGs) were analysed. We identified fourteen hypothetical proteins in mouse hippocampus. Of these, expression levels of 2610008O03Rik protein (Q9D0K2) and 4632432E04Rik protein (Q9D358) were significantly decreased (P < 0.05 and 0.001) and hypothetical protein (Q99KP6) was significantly increased (P < 0.05) in hippocampus of SOD1-TGs as compared with non-transgenic mice. CONCLUSIONS: The biological meaning of aberrant expression of these proteins may be impairment of metabolism, signaling and transcription machinery in SOD1-TGs brain that in turn may help to explain deterioration of these systems in DS brain.