Proteomic and Genomic Endocrine Responses in Oxytocin Knockout Mice

Abstract

Gene knockout animal models have proven extremely useful for studying the effects of a single gene product in systems where human studies are not an option. The nine amino acid peptide, oxytocin, has been shown to play dual roles as a peptide hormone in parturition and milk production; and as a neuropeptide in social and maternal behavior. In this study, we investigated the effect of the absence or presence of a functioning oxytocin allele on other endocrine genes. Taking advantage of an oxytocin-null murine model (OTKO-/-), gene expression levels were assayed for the prohormones; pro-oxytocin, pro-vasopressin, and proopiomelanocortin; processing enzymes, prohormone convertase 1, prohormone convertase 2 and carboxypeptidase E; and transcription factors, c-Fos, and c-Jun in OT+/+ and OTKO-/- animals. Significant changes in gene expression levels were found to occur in cortex and hypothalamic tissues of OTKO-/- mice. Specifically, there was an up-regulation of POMC, PC2, c-Fos and c-Jun in hypothalamus.  PC2 was also found to be up-regulated in the cortex. Western blot analysis of the affected tissues showed similar results. We conclude that the absence of the peptide hormone oxytocin can affect other peptide hormone systems, including processing enzymes and transcription factors.