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This was achieved by replacing the corresponding mouse DNA sequence with a 6\u2010base DNA sequence from the human <jats:italic>CREB1<\/jats:italic> promoter that is associated with MDD in individuals from families with recurrent, early\u2010onset MDD (RE\u2010MDD). In the current study, we explored the effect of the pathogenic <jats:italic>Creb1<\/jats:italic> allele on gene expression in the mouse hippocampus, a brain region that is altered in structure and function in MDD. Mouse whole\u2010genome profiling was performed using the Illumina MouseWG\u20106 v2.0 Expression BeadChip microarray. Univariate analysis identified 269 differentially\u2010expressed genes in the hippocampus of the mutant mouse. Pathway analyses highlighted 11 KEGG pathways: the phosphatidylinositol signaling system, which has been widely implicated in MDD, Bipolar Disorder, and the action of mood stabilizers; gap junction and long\u2010term potentiation, which mediate cognition and memory functions often impaired in MDD; cardiac muscle contraction, insulin signaling pathway, and three neurodegenerative brain disorders (Alzheimer's, Parkinson's, and Huntington's Diseases) that are associated with MDD; ribosome and proteasome pathways affecting protein synthesis\/degradation; and the oxidative phosphorylation pathway that is key to energy production. These findings illustrate the merit of this congenic C57BL\/6 recombinant mouse as a model of RE\u2010MDD, and demonstrate its potential for highlighting molecular and cellular pathways that contribute to the biology of MDD. 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