PACTOLUS AND MAST CELL AND MORROW CELL FUNCTION

描述(改编自调查人员摘要)：细胞的机制 黏附在免疫反应的研究中具有特殊的意义 由于反应的主要成分的独特性质， 循环细胞。大多数器官系统是由细胞组成的，这些细胞的位置 在分化过程中组织内的固定。或者，也可以使用 免疫器官系统由持续存在的细胞类型组成 从骨髓前体获得新的来源，必须寻找选定的位置 在身体内为他们的特定职能。 哺乳动物肥大细胞代表一种细胞，就像它的许多淋巴细胞一样 对应物，占据动物体内的特定位置。因此， 结缔组织肥大细胞选择性地存在于皮肤、肌肉和 腹膜腔内，粘膜肥大细胞主要见于腹膜 胃肠道的粘膜下层、固有层和上皮内间隙 还有呼吸道。 我们已经分离出一种名为Pactolus的新基因，它与 β整合素家族。该基因在成熟期选择性表达。 结缔组织肥大细胞与粘膜肥大细胞的比较。组织的组织 表现出最高水平表达的动物是骨髓。 本申请建议定义Pactolus蛋白的功能 在小鼠体内通过发展一系列免疫学和核 酸基试剂研究其表达，与其他 蛋白质，其作为配体特异性黏附受体的功能，以及它的 成熟结缔组织作为结缔组织归巢受体的可能作用 组织肥大细胞。有人提出了分离人类对应物的研究 并确定人类和小鼠基因在基因组中的位置。这个 通过基因敲除产生缺乏功能性紫杉醇的小鼠品系 此外，还提出了正常基因的同源性。最后的表达方式是 Pactolus认为它的转录在一定程度上受c-kit的控制。 信号转导途径。我们建议分析这一控制途径， 确定Pactolus基因的关键区域 转录诱导和鉴定影响转录的蛋白质 控制力。通过遵循这一实验制度，小鼠紫杉醇的作用 在动物的免疫反应中将被阐明。这些数据将 提供开展类似调查所需的关键信息 人参的角色和功能。

DESCRIPTION (Adapted from Investigator's abstract): The mechanism of cell adhesion takes on special significance in studies of the immune response due to the unique nature of the primary constituents of the response, circulating cells. Most organ systems are comprised of cells whose position within the tissue of fixed during differentiation. Alternatively, the immune organ system consists of cell types that are continually being derived de novo from bone marrow precursors and must seek out selected sites within the body for their specific functions. The mammalian mast cell represents a cell which, like many of its lymphocyte counterparts, occupies specific sites within the animal. Thus the connective tissue mast cell selectively resides within the skin, muscle and peritoneal cavity, and the mucosal mast cell is primarily found within the submucosa, lamina propria and intraepithelial space of the gastrointestinal and respiratory tracts. We have isolated a novel gene, dubbed Pactolus, that is related to the family of beta integrins. The gene is selectively expressed in maturing connective tissue mast cells compared to mucosal mast cells. The tissue of the animal that displays the highest level of expression is the bone marrow. This application proposes to define the function of the Pactolus protein within the mouse by developing a series of immunologic and nucleic acid-based reagents to study its expression, association with other proteins, its function as a ligand-specific adhesion receptor, and its possible role as a connective tissue homing receptor for maturing connective tissue mast cells. Studies are proposed to isolate the human counterpart and to determine the human and murine gene locations in the genome. The generation of mouse strains that lack functional Pactolus via the knockout of the normal gene is also proposed. Finally the expression pattern of Pactolus suggests its transcription is controlled, in part, by a c-kit signal transduction pathway. We propose to analyze this control pathway, identifying regions of the Pactolus gene that are critical for transcriptional induction and identifying the proteins that effect this control. By following this experimental regime, the role of murine Pactolus in the immune response of the animal will be elucidated. These data will provide the key information needed to establish similar investigations into the role and functions of human Pactolus.