Are transgenic mice the ‘alkahest’ to understanding myocardial hypertrophy and failure?
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- 作者：Stuart A. Cook ; Angela Clerk ; Peter H. Sugden
- 关键词：Trangenesis ; Cardioselectivity ; α ; -myosin heavy chain promoter ; Signal strength matching ; End-points ; Intracellular localisation ; Poison proteins ; Genetic background and strain effects ; Glycogen synthase kinase 3 ; Extracellular signal-regulated kinas
- 刊名：Journal of Molecular and Cellular Cardiology
- 出版年：2009
- 出版时间：February 2009
- 年：2009
- 卷：46
- 期：2
- 页码：118-129
- 全文大小：612 K
文摘
Murine transgenesis using cardioselective promoters has become increasingly common in studies of cardiac hypertrophy and heart failure, with expression mediated by pronuclear microinjection being the commonest format. Without wishing to decry their usefulness, in our view, such studies are not necessarily as unambiguous as sometimes portrayed and clarity is not always their consequence. We describe broadly the types of approach undertaken in the heart and point out some of the drawbacks. We provide three arbitrarily-chosen examples where, in spite of a number of often-independent studies, no consensus has yet been achieved. These include glycogen synthase kinase 3, the extracellular signal-regulated kinase pathway and the ryanodine receptor 2. We believe that the transgenic approach should not be viewed in an empyreal light and, depending on the questions asked, we suggest that other experimental systems provide equal (or even more) valuable outcomes.