Tissue Fragility genes in C. elegans

秀丽隐杆线虫的组织脆性基因

• 批准号: 6849124
• 负责人: JOHN D PLENEFISCH
• 金额: $ 21.6万
• 依托单位: UNIVERSITY OF TOLEDO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849124
• 关键词: Caenorhabditis elegans; antibody; biomechanics; cell adhesion; cell cycle; cell growth regulation; extracellular matrix proteins; gene expression; genetic models; green fluorescent proteins; helminth genetics; intercellular connection; intermediate filaments; model design /development; molecular cloning; mutant; protein localization; protein quantitation /detection; skin; tissue support frame

DESCRIPTION (provided by applicant): Using C. elegans as a simple in vivo model, the developmental assembly of hemidesmosome (HD) and intermediate filament (IF) organization is being investigated. The epidermis contains a stress resistant network of IFs through which force can be transmitted. Mutations in mua-2, mua-3, mua-5, and mua-6 all result in a growth and use-dependent fragility of this HD/IF mediated trans-epithelial force transmission pathway. Two of these genes, mua-6 and mua-3, have been cloned and encode an IF and a HD associated protein, respectively. The other two genes, mua-5, and mua-2 whose products are as yet unidentified, have been shown to affect the integrity of these same epidermal complexes. These genes may have human homologues that are involved in the etiology of human diseases, but more importantly, the proposed research continues to develop a simple genetic model in which the biology of matrix receptors, cell adhesion, and their control in development can be studied, impacting on our basic understanding of these interactions in normal development and how they may go awry to cause misattachment or attachment failure in muscular dystrophies, blistering skin diseases and cancers. The long term objective is to understand the cell and molecular biology of HD and IF assembly in growth and development. The short term objective is to ascertain the molecular identity of the products of mua-5 and mua-2 and to understand the potential roles played by them in epidermal tissue integrity and the development of HD/IF complexes. The specific aims are: 1) Clone and identify the predicted products of mua-5, and mua-2 using positional rescue, 2) to identify the cellular and sub-cellular localization of MUA-5 and MUA-2 using GFP fusion constructs and antibodies, 3) to examine the localization of HD associated proteins in mua-2 and mua-5, as well as selected other mutants, and the colocalization of these proteins and MUA-2 and MUA-5 using antibodies and GFP reporters.

描述（由申请人提供）：使用秀丽隐杆线虫作为一个简单的体内模型，正在研究Hemidesmosmosmosmosmosmossmosmosmosmossmosmossmosmossmomsmosmossmos的发展组装和中间细丝（IF）组织。表皮包含一个可以传播力的IF的耐应力网络。 MUA-2，MUA-3，MUA-5和MUA-6中的突变都导致该HD/IF介导的跨上皮力传递途径的生长和使用依赖性脆性。其中两个基因MUA-6和MUA-3分别被克隆并编码一个IF和HD相关蛋白。其他两个基因MUA-5和MUA-2的产物尚未识别，已证明会影响这些相同表皮复合物的完整性。这些基因可能具有与人类疾病病因有关的人类同源物，但更重要的是，拟议的研究继续开发出一种简单的遗传模型，在该模型中，基质受体的生物学，细胞粘附，细胞粘附及其在发育中的控制可以被研究，从而影响我们对这些正常发展和它们可能失败的基本相互作用的基本理解，并使他们在误差中陷入困境，并在穆斯卡上进行了误解。癌症。长期目标是了解HD的细胞和分子生物学以及在生长和发育中的组装。短期目标是确定MUA-5和MUA-2产物的分子身份，并了解它们在表皮组织完整性和HD/IF复合物的发展中所起的潜在作用。具体目的是：1）克隆并使用位置救援识别MUA-5的预测产物和MUA-2，2）使用GFP融合构建体和MUA-5的细胞和亚细胞定位，使用GFP融合构建体和抗体，3）检查MUA-2和MUA-2和MUA-5和MUA-5和MUA-5的CORINITIS的定位，以及其他选择的蛋白质，以及其他选择的蛋白质。以及MUA-2和MUA-5使用抗体和GFP记者。