Core--Myocyte & HF Rabbits

核心--肌细胞

• 批准号: 7139947
• 负责人: Donald M Bers
• 金额: $ 25.33万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7139947
• 关键词: animal colony; biological models; biomedical facility; cardiac myocytes; disease /disorder model; genetically modified animals; heart failure; laboratory mouse; laboratory rabbit; tissue /cell culture

The Core will manage animals (rabbits and mice) from which myocytes will be isolated at Loyola for use in all 4 of the projects. The mice used will include wild type and genetically modified mice that are developed and bred in Core D at UCSD (including some that will be subjected to transverse aortic banding to induce chronic pressure overload in Project by Brown). The rabbits used will include both control and heart failure (HF) rabbits (induced by combined pressure and volume overload). The core will also be responsible for the preparation and functional monitoring of HF rabbits during the evolution of dysfunction (under the direction of Dr. S.M. Pogwizd at UIC). The core will also culture adult cardiac myocytes for 24-48 hours for studies involving adenoviral gene transfer. These myocytes will be used directly by the three Loyola projects (l-lll) for functional, imaging and biochemical analysis and also by Project by Brown for biochemical analysis (after experimental treatment by the investigators at Loyola and shipment to UCSD). The procedures carried out are specialized, but the personnel involved are expert in their respective roles and this should run smoothly and efficiently in making the best use of the myocytes available. Mice are especially valuable because of the opportunity to genetically manipulate the molecules under investigation (and we are taking advantage of that in The Genetic Mouse Models and Adenoviruses Core) and collectively we have extensive experience with mouse myocytes and cardiovascular disease models. The mouse work will be complemented by studies in rabbit, where similar genetic manipulation is not practical, but rabbits are highly advantageous here for two major reasons. First, the electrophysiological and Ca handling properties in rabbit ventricle are very similar to that in human. Second, we have already developed a well-characterized rabbit model of heart failure. Indeed, the HF rabbits manifest both severely depressed LV contractile function and spontaneously-occurring ventricular arrhythmias. Rabbit myocytes are also well suited for the measurements to be made (including: voltage clamp, fluorescence imaging, biochemical and molecular studies, and in vitro adenoviral gene transfer. The services provided by this core are essential to the successful completion of the science in Projects by Bers, Blatter, Mignery, and Brown, enabling the elucidation of mechanistic roles of IP3R and CaMKII in ECC, arrhythmogenesis, hypertrophy and HF.

核心将管理动物（兔子和小鼠），这些动物的肌细胞将在洛约拉分离出来，用于所有 项目4个。使用的小鼠将包括野生型小鼠和经过开发和改造的转基因小鼠。 在 UCSD 的 Core D 中培育（包括一些将接受横主动脉结扎以诱导 布朗项目中的慢性压力超负荷）。使用的兔子将包括对照和心力衰竭（HF） 兔子（由压力和容量超负荷联合诱导）。核心也将负责 HF兔在功能障碍演变过程中的准备和功能监测（在指导下） S.M.博士的UIC 的 Pogwizd）。该核心还将培养成体心肌细胞 24-48 小时进行研究 涉及腺病毒基因转移。这些肌细胞将直接由三个洛约拉项目使用（l-lll） 用于功能、成像和生化分析，也由布朗项目用于生化分析（之后 洛约拉研究人员进行实验性治疗并运送到加州大学圣地亚哥分校）。已执行的程序 是专业的，但所涉及的人员都是各自角色的专家，这应该会顺利进行 并有效地充分利用可用的肌细胞。 小鼠特别有价值，因为它们有机会对分子进行基因操纵 调查（我们正在利用遗传小鼠模型和腺病毒核心），我们拥有丰富的经验 小鼠心肌细胞和心血管疾病模型。鼠标工作将得到补充 在兔子身上进行的研究，类似的基因操作并不实用，但兔子非常有优势 这里有两个主要原因。首先，兔心室的电生理和钙处理特性是 与人类非常相似。其次，我们已经开发了一个特征良好的兔子模型 心脏衰竭。事实上，心力衰竭兔子表现出严重抑制的左心室收缩功能和 自发性室性心律失常。兔肌细胞也非常适合测量 待进行（包括：电压钳、荧光成像、生化和分子研究，以及 体外腺病毒基因转移。该核心提供的服务对于成功至关重要 Bers、Blatter、Mignery 和 Brown 完成的科学项目，能够阐明 IP3R 和 CaMKII 在 ECC、心律失常、肥厚和心力衰竭中的机制作用。