The initiation and maintenance of parturition is a complex process that requires proper function of multiple gene products. To better understand this process, mouse models have been generated that targeted specific known genes. We are interested in the further evaluation of a mouse strain (PART) that was developed by Paul Overbeek, Ph.D. at Baylor College of Medicine using a random insertion/deletion methodology. Preliminary data indicate these mice have a uniquely prolonged/absent parturition that often results in maternal death. Infection is implicated when maternal death occurs. We believe this mouse line offers an opportunity to improve our understanding of the gene (genes) important in transitioning from uterine quiescence into and through labor. We hypothesize that the phenotype of the PART mouse is due to a disruption in a gene (genes) that is important in the initiation and/or maintenance of labor.
In Specific Aim 1, we plan to identify the molecular abnormality created by the insertion/deletion that results in abnormal parturition observed in the PART mouse strain. This information may be useful in further elucidating the underlying etiologies of abnormal parturition during human pregnancy.
In Specific Aim 2, we will also improve our understanding of the physiologic mechanism that underlies abnormal parturition in the PART mouse strain by further characterizing the phenotype and we will attempt to rescue the phenotype with pharmacologic and surgical intervention. These experiments will validate the usefulness of the PART mouse strain as a model of abnormal parturition during pregnancy. If the molecular alteration responsible for the phenotype is determined from Specific Aim 1 to be a previously unrecognized gene (genes), then these experiments will provide the needed information to begin to understand this gene's functional importance in parturition.
