RESISTANT (MDR) GENE IN RODENT MALARIA

啮齿动物疟疾中的耐药（MDR）基因

• 批准号: 6240304
• 负责人: Adelfa E Serrano
• 金额: $ 6.95万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240304
• 关键词: Plasmodium falciparum; SDS polyacrylamide gel electrophoresis; antimalarial agents; communicable disease control; gene expression; immunofluorescence technique; laboratory mouse; laboratory rabbit; malaria; microorganism culture; molecular cloning; multidrug resistance; northern blottings; nucleic acid sequence; pulsed field gel electrophoresis; western blottings

The long term goal of our project is to elucidate the mechanism(s) of drug resistance in Plasmodium spp, particularly, to determine the role played by the multidrug resistance genes (mdr). This subject is of immense biomedical relevance considering the alarming increase in malaria treatment failures resulting from drug resistance. Despite the magnitude of the problem the mechanism(s) of parasite resistance to the majority of antimalarial drugs are not clearly understood. A better understanding of these mechanism(s) would lead to new strategies for the control of the disease. Two mdr-like genes have been identified in P. falciparum, and one of them, the pfmdf1 gene, has been associated with the drug resistance phenotype. However, there is still significant controversy with regard to athe involvement of the pfmdr genes in chloroquine resistance. The P. falciparum model has important limitations for studying the role of these genes, for example only erythrocytic stages could be maintained in vitro and the appropriate animal model, the chimpanzee, is expensive and impractical. The use of rodent malaria clones in vivo (P. berghei and P. yoeli), expressing different patterns of drug sensitivity, provides an excellent model to study the molecular mechanisms of this phenotype. In the present proposal, we will focus our efforts to ascertain the role of the murine multidrug resistance genes in malaria drug resistance. We have shown that mdr-like genes are present in P. berghei and probably, P. yoelii. To determine whether the P. berghei and p. yoelii mdr-homolgues play a role in parasite drug resistance, we will analyze the behavior of these genes at the DNA, RNA, protein and chromosomal level in five P. berghei derived lines and four P. yoelii 17X derived lines expressing different patterns of drug resistance.

我们项目的长期目标是阐明药物的作用机制 疟原虫属的耐药性，特别是确定其所起的作用 多重耐药基因（mdr）。 这个话题意义重大 考虑到疟疾治疗的惊人增加，生物医学相关性 耐药性导致的失败。 尽管事态的严重性 问题是大多数寄生虫的抵抗机制 抗疟药尚不清楚。 更好地理解 这些机制将导致新的控制战略 疾病。 恶性疟原虫中已鉴定出两种 MDR 样基因，一种是 其中 pfmdf1 基因与耐药性相关 表型。 但目前仍存在较大争议 pfmdr 基因参与氯喹耐药性。 P。 恶性疟原虫模型对于研究这些作用具有重要的局限性 基因，例如只能在体外维持红细胞阶段 合适的动物模型——黑猩猩——价格昂贵，而且 不切实际的。 体内啮齿动物疟疾克隆的使用（伯氏疟原虫和伯氏疟原虫） yoeli），表达不同的药物敏感性模式，提供了 研究这种表型的分子机制的优秀模型。 在 在本提案中，我们将重点努力确定 疟疾耐药性中的小鼠多药耐药基因。 我们有 表明 MDR 样基因存在于伯氏疟原虫中，也可能存在于伯氏疟原虫中。 约埃利。 确定 P. berghei 和 P. berghei 是否存在。约埃利多药同系物 在寄生虫耐药性中发挥作用，我们将分析 这些基因在 5 个 P. berghei 衍生品系和四个 P. yoelii 17X 衍生品系表达 不同的耐药模式。