Dilated heart failure in transgenic mice expressing the Epstein-Barr virus nuclear antigen-leader protein.
The Epstein-Barr virus nuclear antigen-leader protein (EBNA-LP) is required for high efficiency B lymphocyte growth transformation by the virus. To test the potential contribution of EBNA-LP to tumorigenesis in vivo, we produced transgenic mice carrying an EBNA-LP cDNA construct, using the widely expressed metallothionein promoter. Expression of EBNA-LP was detected in liver, kidney, heart, lung and spleen. There were no apparent oncogenic consequences of EBNA-LP expression. Unexpectedly however, at ages ranging from about 4 months to over a year, transgenic mice developed symptoms of congestive heart failure, including left ventricular dilatation, right ventricular hypertrophy, left atrial thrombosis, pulmonary oedema and hydrothorax. Fibrillation was not apparent in the electrocardiograph; however a reduction in T-wave amplitude suggested that the development of an abnormality of ventricular repolarization may precede the manifestation of overt symptoms. The highly predictable development of dilated heart failure in these transgenic mice suggests they may be a useful model for the pathophysiological changes associated with human dilated cardiomyopathy.
Huen
D S
DS
Department of Cancer Studies, University of Birmingham Medical School, U.K.
Fox
A
A
Kumar
P
P
Searle
P F
PF
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D015139:Blotting, Southern; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D004562:Electrocardiography; D019309:Epstein-Barr Virus Nuclear Antigens; D013006:Growth Hormone / Q000235:genetics; D006321:Heart / Q000503:physiopathology; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D009928:Organ Specificity; D021382:Protein Sorting Signals / Q000096:biosynthesis* / Q000235:genetics; D015183:Restriction Mapping
D000956:Antigens, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D021382:Protein Sorting Signals; D013006:Growth Hormone; D008668:Metallothionein