Cardiac expression of Gal4 causes cardiomyopathy in a dose-dependent manner.
Cardiac expression of a transgene is a common approach for determining the role of gene products in the processes underlying cardiomyopathy and heart failure (HF). We have generated transgenic mice that express the 'harmless' yeast transcription factor Gal4 in the heart under control of the alpha-myosin heavy chain promoter and found that expression of this gene causes cardiomyopathy and HF, the severity of which correlated with the number of copies of the transgene integrated into the genome and with the expression level. A line with a single copy of the transgene targeted to the hprt locus correctly expressed the transgene but did not develop cardiomyopathy. Our results indicate that expression of a transgene in the heart may non-specifically cause HF in a dose-dependent manner.
Habets
Petra E M H
PE
Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Clout
Danielle E W
DE
Lekanne Deprez
Ronald H
RH
van Roon
Marian A
MA
Moorman
Antoon F M
AF
Christoffels
Vincent M
VM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology; D018031:Connexin 43 / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D018628:Gene Dosage; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006325:Heart Atria / Q000737:chemistry / Q000378:metabolism; D006333:Heart Failure / Q000235:genetics / Q000473:pathology; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D018994:Myosin Light Chains / Q000235:genetics; D009929:Organ Size / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation; D024723:Ventricular Myosins / Q000235:genetics
D018031:Connexin 43; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; D018994:Myosin Light Chains; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C107184:myosin light chain 2; D009320:Atrial Natriuretic Factor; D024722:Cardiac Myosins; D024723:Ventricular Myosins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases