Oxytocin is a peptide hormone, produced in the hypothalamus and in various reproductive organs, that is proposed to be a major regulator of reproductive physiology and behavior. It is the principal initiator of lactation and plays an important role as a stimulant for labor in the clinical setting. In addition, much evidence has accumulated to suggest that oxytocin is essential for maternal behavior and important in sexual behavior. Methodologies available to date to examine oxytocin's roles have been limited because of the inability to convincingly eradicate all oxytocin synthesis, both in the nervous system and in peripheral reproductive organs. In order to clarify oxytocin's functions, a murine model of oxytocin deficiency has been created using the technique of targeted gene inactivation. Initially, this new oxytocin-deficient strain will require full characterization, verifying the absence of oxytocin production and the integrity of synthesis of other hypothalamic hormones. Growth will be evaluated by comparison with wild-type littermates from heterozygote matings. Histologic methods will be used to study organogenesis. The ability of the oxytocin-deficient mouse to reproduce will be examined in detail, including evaluation of libido, fertility, parturition, breast-feeding, and maternal behavior, in all of which oxytocin has been implicated to play a major role. Parturition and lactation, the two functions most likely to be altered by oxytocin deficiency, will be further manipulated by pharmacologic interventions, both to replace oxytocin and to interfere with other potential hormonal modulators. Clinically, this model will answer questions about the control of parturition and provide new insights into ways to intervene with premature and other dysregulated labor. The candidate has an extensive background in molecular biology and cell culture techniques obtained during graduate and postdoctoral work. The goal in this project will be to provide a thorough grounding in histologic, physiologic and behavioral methods, under the experienced mentorship of her sponsor, Joseph Majzoub, and her collaborator, Louis Muglia, which will serve the candidate well as she pursues a career as an independent investigator in academic medicine. The resources, in terms of equipment, animal facilities, and personnel available for learned consultation, are rich within the Division of Endocrinology, not to mention at Children's Hospital as a whole.
