Are transgenic mice the 'alkahest' to understanding myocardial hypertrophy and failure?
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.
Cook
Stuart A
SA
NHLI Division, Faculty of Medicine, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK.
Clerk
Angela
A
Sugden
Peter H
PH
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism
D019837:Ryanodine Receptor Calcium Release Channel; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3