Functional analysis of a novel, stress-inducible transcript in the mouse brain

Aiming at the identification of novel stress regulated genes we studied the effects of 24 hours maternal separation on gene expression in the PVN of neonatal mice using a microarray approach. Among the most strongly regulated genes, we discovered a novel transcript of unknown function (working name MPIP101), showing a pronounced upregulation after maternal separation. This gene codes for a short protein conserved throughout many species. The aim of this study is the functional analysis of gene expression and regulation in neonatal and adult mouse brain. In neonate mice, GR-antagonist treatment prevented the stress induced upregulation of MPIP101 in the PVN, indicating a GR dependent gene regulation. This finding is in line with a promoter analysis of the gene, which revealed several functional GRE sites. In adult mice MPIP101 is strongly expressed in the hippocampal CA3 region, in the cortex and the cerebellum, with low basal expression in the PVN. Dexamethasone treatment and food deprivation resulted in a profound induction of gene expression in the PVN. Hippocampal overexpression in vivo using an adeno-associated viral vector revealed improved cognitive flexibility in the morris water maze as well as active stress-coping behavior in the forced swim test. Further MPIP101 overexpression was found to modulate electrophysiological properties of the hippocampus. In ongoing studies, we will analyze the cellular localization of the protein and the interaction with other proteins.