CREATION OF CLONED CATTLE LACKING THE PRION GENE

缺乏朊病毒基因的克隆牛的创造

• 批准号: 2792696
• 负责人: JOSE B CIBELLI
• 金额: $ 9.97万
• 依托单位: OCATA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2792696
• 关键词: animal tissue; cow; electroporation; gene expression; gene targeting; genetic strain; genetically modified animals; molecular cloning; nuclear transfer; prions; spongiform encephalopathy; transfection /expression vector

Bovine spongiform encephalopathy (BSE) is a world-wide problem for consumers of agriculture, industrial and medical products. An altered form of the prion (PrP) gene appears to be the causative agent, and an endogenous PrP gene is necessary for infection. Advanced Cell Technology and the University of Massachusetts recently announced the birth of three cloned transgenic calves, George, Charlie and Albert. In phase I of this project, we will extend this work, by creating a targeting vector for the bovine prion gene,, PrP, and optimizing the conditions for electroporation and drug selection in bovine embryonic fibroblasts cells. In phase II, we will create BEF cells and cattle containing a homologously-targeted PrP gene. Based on evidence from PrP knockout mice, we hypothesize that are cloned transgenic animals will be unable to both transmit and contract the prion-based disease, BSE. Thus, the long term goal of this project is to create a strain of cattle to be used: (1) to study PrP function in cattle, (2) as a source of prion-free embryonic tissue to treat neurodegenerative disease (3) to increase the safety profile of bovine derived products for research and pharmaceuticals, and (4) as a source of prion-free food products for consumers. PROPOSED COMMERCIAL APPLICATIONS: Cattle containing a targeted deletion of prion protein can be used commercially (1) as a source of prion-free embryonic tissue to treat neurodegenerative disease (2) to increase the safety profile of bovine-derived products (3) as a source of prion-free food products

牛海绵状脑病（BSE）是一个世界性的问题，消费者的农业，工业和医疗产品。朊病毒（PrP）基因的改变形式似乎是病原体，内源性PrP基因是感染所必需的。先进细胞技术公司和马萨诸塞州大学最近宣布了三头克隆转基因小牛的诞生，它们是乔治、查理和阿尔伯特。在本项目的第一阶段，我们将通过创建牛朊病毒基因PrP的靶向载体并优化牛胚胎成纤维细胞中电穿孔和药物选择的条件来扩展这项工作。在第二阶段，我们将创建BEF细胞和牛含有同源靶向PrP基因。基于PrP基因敲除小鼠的证据，我们假设克隆的转基因动物将不能传播和感染基于朊病毒的疾病BSE。因此，本项目的长期目标是创建一个牛品系，用于：（1）研究牛中的PrP功能，（2）作为无朊病毒胚胎组织的来源治疗神经退行性疾病，（3）增加牛源产品用于研究和药物的安全性，以及（4）作为消费者无朊病毒食品的来源。拟议的商业应用：含有朊病毒蛋白质靶向缺失的牛可在商业上（1）作为无朊病毒胚胎组织的来源，以治疗神经变性疾病（2）增加牛源产品的安全性（3）作为无朊病毒食品的来源