Analysis of gene expression and regulation of a novel, stress-inducible transcript in the mouse

• Published in: Pharmacopsychiatry
• Main Authors: Liebl, C, Schülke, J, Schmidt, MV, Trümbach, D, Rein, T, Müller, MB
• Format: Conference Proceeding
• Language: English
• Published: 08.10.2007
• ISSN: 0176-3679; 1439-0795
• DOI: 10.1055/s-2007-991869

We studied the effects of 24 hours maternal deprivation on gene expression in the PVN of 9 day-old mice using microarray technology. Among the strongest regulated genes we discovered a novel transcript (interim name MPIP-101), which showed a pronounced upregulation in the maternal deprived group. This gene codes for a short hypothetical protein of unknown function that has also a human ortholog. The aim of the current study is the functional analysis of the expression and regulation of this gene in neonatal and adult mouse brain. In the neonate, GR-antagonist treatment prevented an maternal deprivation induced upregulation of MPIP-101 mRNA in the PVN, indicating a GR dependant gene regulation. This finding is in line with a promoter analysis of this gene, which revealed several functional GRE sites. In conditional CRHR1 knockout mice the maternal deprivation induced upregulation of MPIP-101 was significantly reduced, suggesting an additional regulatory mechanism via CRH mediated pathways. In adult mice MPIP-101 is mostly expressed in the CA3 region of the hippocampus, in the cortex and the cerebellum, with very little expression in the PVN under basal conditions. Dexamethasone treatment, restraint stress and food deprivation result in a profound induction of gene expression in the PVN, confirming the data of the neonate. In ongoing studies we analyze the cellular localization of MPIP-101, its interaction with other proteins and co-localization with central stress markers.