MOLECULAR TOOLS TO DEVELOP HAMSTER MODELS OF DISEASE

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The Syrian hamster (Mesocricetus auratus) has unique features that make it advantageous for use as a model for a number of infectious, cardiopulmonary, inflammatory, and neoplastic diseases. Substantive work has been performed using the hamster to study these disease models, but investigations into the molecular nature of the disease processes have been hindered by the lack of available reagents. In particular, studs' of diseases in which the pathogenesis involves immunologic or inflammatory mechanisms has been severely limited. The overall objective of this proposed applied research is to develop molecular tools that will enable the further development of the hamster as a model of human infectious, cardiopulmonary, inflammatory, and neoplastic disease. Because of the hamster's genetic divergence from mice and rats, there are very few immunological reagents used for mouse and rat studies which can also be used in the study of hamster models of disease. In this proposed research we will clone and express several hamster cytokine and chemokine cDNAs which have been shown in humans and animal models to play a critical role in the regulation and effector activity of the host immune and inflammatory' responses. We will then develop anti-cytokine and antichemokine antibody reagents that can be used in these models to detect, quantify, and neutralize these molecules. The development of this core of immunological reagents specifically for the hamster will have broad application to the development of models of disease in this animal. This work will have particular relevance to research traditionally funded through a number of NIH institutes including the NCI, NIAID, NHLBI, NIA, NIAMS, and NIDR.