MOLECULAR TOOLS TO DEVELOP HAMSTER MODELS OF DISEASE

叙利亚仓鼠（Mesocricetus auratus）具有独特的功能，使其有利于作为一个模型的一些感染性，心肺，炎症和肿瘤性疾病。已经进行了大量的工作，使用仓鼠来研究这些疾病模型，但由于缺乏可用的试剂，对疾病过程的分子性质的研究受到阻碍。特别是，对发病机制涉及免疫或炎症机制的疾病的研究受到严重限制。这项拟议的应用研究的总体目标是开发分子工具，使仓鼠作为人类感染性，心肺，炎症和肿瘤疾病的模型的进一步发展。由于仓鼠与小鼠和大鼠的遗传差异，用于小鼠和大鼠研究的免疫学试剂很少也可用于仓鼠疾病模型的研究。在这项拟议的研究中，我们将克隆和表达几种仓鼠细胞因子和趋化因子的cDNA，这些cDNA已在人类和动物模型中显示出在宿主免疫和炎症反应的调节和效应活性中起关键作用。然后，我们将开发抗细胞因子和抗趋化因子抗体试剂，可用于这些模型中检测，定量和中和这些分子。专门用于仓鼠的这种核心免疫试剂的开发将广泛应用于该动物疾病模型的开发。这项工作将特别相关的研究传统上通过一些NIH研究所，包括NCI，NIAID，NHLBI，NIA，NIAMS和NIDR资助。

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.