Tarnavski Oleg, McMullen Julie R, Schinke Martina, Nie Qing, Kong Sekwon, Izumo Seigo
Cardiovascular Research Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Physiol Genomics. 2004 Feb 13;16(3):349-60. doi: 10.1152/physiolgenomics.00041.2003.
Mouse models mimicking human diseases are important tools in trying to understand the underlying mechanisms of many disease states. Several surgical models have been described that mimic human myocardial infarction (MI) and pressure-overload-induced cardiac hypertrophy. However, there are very few detailed descriptions for performing these surgical techniques in mice. Consequently, the number of laboratories that are proficient in performing cardiac surgical procedures in mice has been limited. Microarray technologies measure the expression of thousands of genes simultaneously, allowing for the identification of genes and pathways that may potentially be involved in the disease process. The statistical analysis of microarray experiments is highly influenced by the amount of variability in the experiment. To keep the number of required independent biological replicates and the associated costs of the study to a minimum, it is critical to minimize experimental variability by optimizing the surgical procedures. The aim of this publication was to provide a detailed description of techniques required to perform mouse cardiac surgery, such that these models can be utilized for genomic studies. A description of three major surgical procedures has been provided: 1) aortic constriction, 2) pulmonary artery banding, 3) MI (including ischemia-reperfusion). Emphasis has been placed on technical procedures with the inclusion of thorough descriptions of all equipment and devices employed in surgery, as well as the application of such techniques for expression profiling studies. The cardiac surgical techniques described have been, and will continue to be, important for elucidating the molecular mechanisms of cardiac hypertrophy and failure with high-throughput technology.
模拟人类疾病的小鼠模型是试图理解许多疾病状态潜在机制的重要工具。已经描述了几种模拟人类心肌梗死(MI)和压力超负荷诱导的心脏肥大的手术模型。然而,关于在小鼠中执行这些手术技术的详细描述非常少。因此,精通在小鼠中进行心脏手术程序的实验室数量有限。微阵列技术可同时测量数千个基因的表达,从而能够识别可能潜在参与疾病过程的基因和通路。微阵列实验的统计分析受到实验中变异性大小的高度影响。为了将所需的独立生物学重复数量以及研究的相关成本降至最低,通过优化手术程序将实验变异性降至最低至关重要。本出版物的目的是提供执行小鼠心脏手术所需技术的详细描述,以便这些模型可用于基因组研究。已提供了三种主要手术程序的描述:1)主动脉缩窄,2)肺动脉环扎,3)心肌梗死(包括缺血再灌注)。重点在于技术程序,包括对手术中使用的所有设备和装置的详细描述,以及此类技术在表达谱研究中的应用。所描述的心脏手术技术对于通过高通量技术阐明心脏肥大和衰竭的分子机制一直并且将继续具有重要意义。