Dilated heart failure in transgenic mice expressing the Epstein--Barr virus nuclear antigen-leader protein

Huen, David; Fox, Andrew; Kumar, Prem; Searle, Peter F.

doi:10.1099/0022-1317-74-7-1381

Cited by 13 publications

(7 citation statements)

References 30 publications

(26 reference statements)

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“…This finding suggested that the unique pathology reflected expression that actually was restricted to kidney cells. In contrast, the expression of the EBV leader protein induced heart failure but did not induce tumors (37). A single study has succeeded in expressing an EBV protein in lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Expression of the Epstein–Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice

Kulwichit

Edwards

Davenport

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

362

258

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The latent membrane protein 1 (LMP1) of the Epstein-Barr virus has transforming properties in rodent fibroblasts and is expressed in most of the cancers associated with Epstein-Barr virus (EBV) infection including posttransplant lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, and AIDS-related lymphomas. In this study, three lineages of LMP1 transgenic mice were established with LMP1 expressed under the control of the Ig heavy chain promoter and enhancer. Lymphoma developed in all three lineages, and the incidence of lymphoma increased significantly with age with lymphomas developing in 42% of transgenic mice over 18 months. The expression of LMP1 was detected at high levels in the lymphoma tissues but only at trace levels in normal lymphoid tissues. Gene rearrangement of the Ig heavy chain indicated monoclonality or oligoclonality in all lymphomas, some of the lymphoid hyperplastic spleens, and some histologically normal spleens. These data reveal that LMP1, without the expression of other EBV genes, is oncogenic in vivo and indicate that LMP1 is a major contributing factor to the development of EBV-associated lymphomas.

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Section: Discussionmentioning

confidence: 99%

Expression of the Epstein–Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice

Kulwichit

Edwards

Davenport

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

362

258

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“…The Epstein-Barr virus nuclear antigen-leader protein (EBNA-LP) is required for high-efficiency B lymphocyte growth transformation by the virus. Transgenic mice carrying the EBNA-LP also unexpectedly develop congestive cardiac failure with ventricular dilatation and abnormalities of the ventricular repolarization process [53].…”

Section: Transcription Factorsmentioning

confidence: 99%

“…Calmodulin levels decline during the early postnatal stages in close association with the diminishing population of proliferative cardiocytes, suggesting that calmodulin may influence myocyte proliferation. A targeted model with a cardiac overexpression of calmodulin was produced by Gruver [53]. The developmental expression was, as expected with such a promoter, characterized by abundant atrial and ventricular levels of calmodulin during gestational and early postnatal developmental stages in carrier offspring.…”

Section: Othersmentioning

confidence: 99%

Transgenic models of myocardial dysfunction

Swynghedauw

1997

Heart Failure Rev

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Transgenic Technology (TT), is an important tool in the molecular biology arena. It allows one to generate new strains of mice in which a genetic construct is expressed. The construct can be made with a promoter that allows for the targeted expression of a gene of interest to a given part of the cardiovascular system. By so doing, it is possible to modify a given physiologic function and to better understand the structural and functional relationships. This so-called "reverse physiology" is becoming extensively utilized in cardiac research. Another possibility is to use this technology to analyze which part of a promoter is responsible for the transcriptional regulation. In that case, the coding sequence is a gene not normally expressed in the tissue and is called the reporter. Mice are generally used for such a purpose because of their cost. Consequently the physiology of the mouse has been developed using microtechnologies.Several models of cardiac hypertrophy or tumors have been developed using genes encoding various transcriptional factors, such as oncoproteins or skeletal myogenic regulators. The overexpression of the two ~-Adrenergic Receptors (AR), did not generate hypertrophy, while that of al~-AR did. Myocardial function has been studied after disruption or overexpression of genes known to be vital to the functioning of the myocardium. Disruption of phospholamban results in increased relaxation and contractility. The overexpression of both the ~1-and ~2-AR increases basal contractility, which becomes insensitive to isoproterenol. We have also found in our laboratory that the enhanced ~I-AR model has an impaired heart rate variability without arrhythmias or shortening of the life span. An overexpression of Gs~ or ~-AR kinase does not have any inotropic effect per se, but results in an enhanced inotropic and chronotropic effect of isoproterenol. Such experiments have been the basis of new concepts in receptology. Several transgenic models of arterial hypertension with cardiac hypertrophy are now available. Most of them have been created by transgenic manipulations of the renin-angiotensin system. For the moment, there are only a few transgenic models of cardiac failure available.can synthesize DNA or RNA fragments and use them to make proteins or detect rapid changes in the cardiac or vascular structures. Soon after, molecular biologists could not resist the fascinating experiment inherent in introducing a new genetic material into germinal, autosomal, and even in adult cells. This was done in order to change genetic expression, with the ultimate goal of either permanently or transiently, modifying the phenotype of a cell, of a group of cells, and finally of an entire organism.Gene transfer technologies are currently a source of heated debate in cardiovascular research. These technologies offer promising areas for therapeutic approaches, such as the prevention of restenosis after coronary angioplasty. Nevertheless, the time when DNA can be a real drug is unpredictable. In contrast, these technologies, and ...

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“…1 Mutations in dystrophin (3) and myotonin protein kinase (4) have been linked to familial DCM associated with Becker/Duchenne muscular dystrophy and myotonic dystrophy. Loss-of-function studies with muscle LIM protein (5) and desmin-(6) deficient mice, or gain-of-function analysis in transgenics overexpressing diverse gene products, such as polyoma virus large T (7), Epstein-Barr virus nuclear antigen-leader protein (8), and G s ␣ (9), can also reproduce aspects of DCM.…”

Section: Introductionmentioning

confidence: 99%

Cardiac compartment-specific overexpression of a modified retinoic acid receptor produces dilated cardiomyopathy and congestive heart failure in transgenic mice.

Colbert¹,

Hall²,

Kimball³

et al. 1997

J. Clin. Invest.

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Retinoids play a critical role in cardiac morphogenesis. To examine the effects of excessive retinoid signaling on myocardial development, transgenic mice that overexpress a constitutively active retinoic acid receptor (RAR) controlled by either the ␣ -or ␤ -myosin heavy chain (MyHC) promoter were generated. Animals carrying the ␣ -MyHC-RAR transgene expressed RARs in embryonic atria and in adult atria and ventricles, but developed no signs of either malformations or disease. In contrast, ␤ -MyHC-RAR animals, where expression was activated in fetal ventricles, developed a dilated cardiomyopathy that varied in severity with transgene copy number. Characteristic postmortem lesions included biventricular chamber dilation and left atrial thrombosis; the incidence and severity of these lesions increased with increasing copy number. Transcript analyses showed that molecular markers of hypertrophy, ␣ -skeletal actin, atrial natriuretic factor and ␤ -MyHC, were upregulated. Cardiac performance of transgenic hearts was evaluated using the isolated perfused working heart model as

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Dilated heart failure in transgenic mice expressing the Epstein--Barr virus nuclear antigen-leader protein

Cited by 13 publications

References 30 publications

Expression of the Epstein–Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice

Expression of the Epstein–Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice

Transgenic models of myocardial dysfunction

Cardiac compartment-specific overexpression of a modified retinoic acid receptor produces dilated cardiomyopathy and congestive heart failure in transgenic mice.

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