Mouse Modeling Core

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Introduction to Revised Core C: We greatly appreciate the positive comments of the reviewers regarding the Mouse Modeling Core facility. We have responded to the issues raised, as outlined below, and would also like to draw attention an important addition to our Core services. We have very recently described a new experimental endometriosis model, using Rag2y(c) mice (Bruner-Tran et al, 2006b). Due to the severity of the immune defects of this immunosuppressed mouse strain, we have been able to transfer both human immune and endometrial cells to this animal, allowing examination of the potential role of immune cells in the pathophysiology of endometriosis. Although this model has not yet been fully characterized, we anticipate completing these studies within the next 12 months and making this model available to Center investigators immediately thereafter. We believe this model system will be a valuable addition to the Mouse Modeling Core which should aid our understanding both the development and treatment of endometriosis. ¿ 1. Past experience or a plan describing assessment of successful engraftment of shipped samples was not discussed. This information has now been included within the Core description. Specifically, the Core lab has previously examined the effect of overnight shipment of fresh tissues prior to engraftment into mice and we have found no noticeable difference between size or number of lesions compared to tissues that were not shipped. Additionally, we have previously demonstrated that tissues can be pre-cultured for up to 48 hrs (versus the typical 24 hrs) without noticeable impact on cell survival or lesion implantation rate further supporting the feasibility of shipping tissues overnight and then culturing 24 hrs prior to introduction into mice. 2. Communication between the PLs at Yale and the Core lab will be critical and should be discussed in more detail. As now detailed within the Core description, Drs. Osteen and Bruner-Tran have extensive experience conducting studies as an "off-site" location for our collaborators. We foresee no difficulties in working with investigators at Yale. 3. There was little discussion regarding the role of internal and external review groups in oversight of the Core. External review will be conducted twice each year, alternating between Vanderbilt and Yale. Yale's internal review group will additionally visit the Vanderbilt sites (the Mouse Core and Dr. Osteen's laboratory) at regular intervals. Highlighting of Changes/Corrections: Sections of this application which are significantly altered from the previous submission have been indicated by the presence of a bold line to the left of the text, as present to the left of this paragraph.