The purpose of the Animal Core Facility [ACF] is to provide support for the research projects [Projects 1, 2, and 3] proposed in this program project grant that will use animals. The ACF has been actively engaged in developing animal models for AIDS and AIDS-associated malignancies. This has been especially evident in the development of the nude mouse for studying the pathogenesis and development of novel therapies for Kaposi's Sarcoma [KS]. Additionally, we have developed a strong transgenic animal model program which includes the use, and continued characterization, of the HIV-1 transgenic mouse. The ACF also has expertise and experience in working with the SIV monkey model for AIDS studies. We now want to expand these studies to build on our finds of the relationship of Tat, the protein product of HIV, host cytokines, and more recently the relationship of KS-associated herpes virus [KSHV], or HHV8, to KS. In the proposed project, the ACF will provide the expertise for injecting KS cells into mice for tumor production, cytokine studies for testing human chorionic gonadotropin [hCG]-associated factors [HAF] and pregnant urine factors on KS, and for anti-angiogenesis factors to be studied using the rat cornea model. In addition, the ACF will produce lines of transgenic mice with various constructs of HHV-8. Our long-term objective is to continue to develop these models for studies of KS pathogenesis and therapy. These studies will enhance our understanding of the interactions of viral genes and host factors on KS development and the mechanisms of how HAF factors block and kiss KS tumors. Our ultimate goal is to use these models to develop therapies for use in AIDS patients with KS. The ACF is fully equipped and staffed to support the aims in this proposal and will allow for efficiency and cost benefit for the overall program project grant [PPG] with regard to animal use.
