动物造模,基因修饰性心力衰竭模型 z-bio 2021-04-08 380

　　Adult mice exhibit hemodynamic and clinical manifestations similar to human HF. Therefore, using gene knockout or transgenic mouse models to change the expression of specific genes in the heart, to study the role and mechanism of specific genes in the development of heart and heart failure, will study the cause of heart failure. Determine new treatment goals. Valuable tool.

　　[Modeling mechanism] In theory, gene recombination technology is used to overexpress specific factors in the myocardium, and gene knockout technology is used to delete genes closely related to myocardial contractility, which can lead to heart failure. Mouse genes are similar to humans and are easy to modify, and the expression of modified genes is relatively stable. Currently, gene knock-in, knock-out and interference technologies can be used to alter the expression of specific genes in the heart, thereby establishing a mouse model of transgenic heart failure.

　　[Model Features] Muscle limbic protein knockout mice: Muscle LIM protein (MLP) regulates muscle differentiation. Homozygous mice whose MLP gene has been deleted have a phenotype similar to diastolic cardiomyopathy and cause cardiac hypertrophy and stromal cell proliferation. Fibrosis develops into HF after adulthood, and its hemodynamics and clinical manifestations are similar to human HF. It is characterized by left ventricular dysfunction and death. Musclelim protein knockout mice are used as genetic models of heart failure in many laboratories to explore molecular therapies for heart failure and dilated cardiomyopathy. Calmodulin kinase II transgenic mice: Calmodulin kinase II (Calmodulin Kinase II, CaMKII) has significantly increased activity and expression of heart failure. The heart of transgenic mice overexpressed the cytoplasmic subtype of CaMKII, left ventricular hypertrophy and left ventricular dilatation were observed, and heart failure gradually developed.

　　Actin gene transgenic mice: Actin gene transgenic mice (mActin-Tg, a mutant gene reported in patients with dilated cardiomyopathy), the left ventricle of the mouse gradually expands and becomes dysfunctional, and finally suffers from heart failure. Risk of death.

　　1-aminocyclopropane-1-carboxylic acid synthase 1 transgenic mouse: The myosin heavy chain gene promoter 1 was used to overexpress 1-aminocyclopropane-1-carboxylic acid synthase in the heart of the transgenic mouse 1. A mouse model of metabolic myosin can be established. [Model Evaluation and Application] Musclelim protein knockout mice are used as gene models of heart failure and can be used to explore molecular therapies for heart failure and dilated cardiomyopathy. The 1-aminocyclopropane-1-carboxylic acid synthase 1 transgenic mouse model can be used as a HF model with abnormal lipid metabolism, which helps to clarify the cellular mechanism of lipotoxic HF, and conduct pharmacological experiments and gene rescue studies. Thereby providing a model. strategy. The genetically modified heart failure model can also be used to understand genes related to heart failure and provide a basis for gene therapy. Its disadvantage is that it cannot fully reflect the true etiology and pathology of patients with heart failure in clinical practice.