PACTOLUS AND MAST CELL AND MORROW CELL FUNCTION

PACTOLUS、肥大细胞和莫罗细胞功能

• 批准号: 2887616
• 负责人: John Weis
• 金额: $ 20.27万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2001-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887616
• 关键词: biological signal transduction; bone marrow; cell adhesion; cell differentiation; cell type; flow cytometry; gene expression; gene targeting; genetic enhancer element; genetic mapping; genetic promoter element; genetic transcription; hematopoiesis; immunoprecipitation; integrins; laboratory mouse; mast cell; protein localization; protein structure function; protooncogene

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.

描述（改编自研究者的摘要）：细胞的机制 粘附在免疫反应研究中具有特殊意义 响应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，其位置 在分化过程中固定在组织内。 或者， 免疫器官系统由不断被破坏的细胞类型组成 从骨髓前体衍生而来，必须寻找选定的位点 在体内发挥其特定功能。 哺乳动物肥大细胞代表一种细胞，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存在于皮肤、肌肉和 腹膜腔，粘膜肥大细胞主要存在于腹膜腔内 胃肠粘膜下层、固有层和上皮内间隙 和呼吸道。 我们分离出了一种新基因，称为 Pactolus，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相比。 的组织 显示最高表达水平的动物是骨髓。 该申请旨在定义 Pactolus 蛋白的功能 通过在小鼠体内开发一系列免疫学和核酸 酸基试剂来研究其表达以及与其他物质的关联 蛋白质，其作为配体特异性粘附受体的功能及其 作为成熟结缔组织归巢受体的可能作用 组织肥大细胞。 建议进行研究以分离人类对应物 并确定人类和小鼠基因在基因组中的位置。 这 通过基因敲除产生缺乏功能性 Pactolus 的小鼠品系 还提出了正常基因的相关性。 最后的表达模式为 Pactolus 表明其转录部分由 c-kit 控制 信号转导途径。 我们建议分析这个控制途径， 识别对 Pactolus 基因至关重要的区域 转录诱导并鉴定影响此的蛋白质 控制。 通过遵循这一实验方案，小鼠 Pactolus 的作用 将阐明动物的免疫反应。 这些数据将 提供开展类似调查所需的关键信息 人类 Pactolus 的作用和功能。