PACTOLUS AND MAST CELL AND MORROW CELL FUNCTION

描述（改编自研究者摘要）：细胞机制 粘附在研究免疫应答中具有特殊意义， 反应的主要成分的独特性质， 循环细胞 大多数器官系统由细胞组成， 在分化期间固定的组织内。 或者， 免疫器官系统由不断被 从骨髓前体重新衍生，必须寻找选定的位点， 在身体中发挥其特定的功能。 哺乳动物的肥大细胞与许多淋巴细胞一样， 对应物，占据动物体内的特定部位。 因此 结缔组织肥大细胞选择性地驻留在皮肤、肌肉和 腹腔，粘膜肥大细胞主要存在于 胃肠道的粘膜下层、固有层和上皮内间隙 和呼吸道。 我们已经分离出一个新的基因，称为Pactolus，这是有关的 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相比。 的组织 表现出最高水平表达的动物是骨髓。 本申请提出定义Pactolus蛋白的功能 在小鼠体内通过开发一系列免疫和核酸 酸基试剂，以研究其表达，与其他 蛋白质，其作为配体特异性粘附受体的功能，及其 作为成熟结缔组织的结缔组织归巢受体的可能作用 组织肥大细胞 研究人员建议将人类的对应物 并确定人类和鼠基因在基因组中的位置。 的 通过敲除产生缺乏功能性Pactolus的小鼠品系 正常基因的表达。 最后， Pactolus认为它的转录部分由c-kit控制 信号转导途径 我们建议分析这种控制途径， 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 通过遵循该实验方案，小鼠Pactolus的作用 动物的免疫反应将被阐明。 这些数据将 提供建立类似调查所需的关键信息， 人类Pactolus的作用和功能。

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.