Manipulating the contractile apparatus: genetically defined animal models of cardiovascular disease.
Within the last 10 years via gene targeting and transgenesis, numerous models of cardiovascular disease have been established and used to determine if a protein's presence or absence causes cardiovascular disease. By affecting the heart's protein complement in a defined manner, the function of the different mutated proteins or protein isoforms present in the contractile apparatus can be determined and pathogenic mechanism(s) explored. We can now remodel the cardiac protein profile and effect replacement of even the most abundant contractile proteins. Precise genetic manipulation allows exploration of the structure-function relationships which underlie cardiac function, and the consequences of defined mutations at the molecular, biochemical, cytological and physiologic levels can be determined.
Dalloz
F
F
Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA.
Osinska
H
H
Robbins
J
J
D000818:Animals; D030801:Animals, Genetically Modified; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D003285:Contractile Proteins / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D005544:Forecasting; D018390:Gene Targeting; D005799:Genes, Dominant; D006801:Humans; D006984:Hypertrophy; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009154:Mutation; D009200:Myocardial Contraction / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000172:deficiency / Q000235:genetics; D018994:Myosin Light Chains / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D010210:Papillary Muscles / Q000473:pathology; D010641:Phenotype; D021122:Protein Subunits; D012518:Sarcomeres / Q000378:metabolism; D014335:Tropomyosin / Q000737:chemistry / Q000172:deficiency / Q000502:physiology; D019210:Troponin I / Q000737:chemistry / Q000172:deficiency / Q000502:physiology; D020107:Troponin T / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D003285:Contractile Proteins; D018995:Myosin Heavy Chains; D018994:Myosin Light Chains; D021122:Protein Subunits; D014335:Tropomyosin; D019210:Troponin I; D020107:Troponin T; D000099163:Myosin Binding Protein C