Transgenic model of cardiac rhabdomyosarcoma formation

Köbbert, Christiane; Möllmann, Christa; Schäfers, Michael; Hermann, Sven; Baba, Hideo A.; Hoffmeier, Andreas; Breithardt, Günter; Scheld, Hans H.; Weissen–Plenz, Gabriele; Sindermann, Jürgen R.

doi:10.1016/j.jtcvs.2008.04.022

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 136, Issue 5 , Pages 1178-1186, November 2008

Transgenic model of cardiac rhabdomyosarcoma formation

Christiane Köbbert, PhD
- Department of Cardiology and Angiology, Hospital of the University of Münster, Münster, Germany
- Leibniz Institute for Arteriosclerosis Research, the University of Münster, Münster, Germany
Christa Möllmann
- Department of Cardiology and Angiology, Hospital of the University of Münster, Münster, Germany
- Leibniz Institute for Arteriosclerosis Research, the University of Münster, Münster, Germany
Michael Schäfers, MD
- Department of Nuclear Medicine, Hospital of the University of Münster, Münster, Germany
Sven Hermann, MD
- Department of Nuclear Medicine, Hospital of the University of Münster, Münster, Germany
Hideo A. Baba, MD
- Institute of Pathology, Hospital of the University of Duisburg-Essen, Essen, Germany
Andreas Hoffmeier, MD
- Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Münster, Germany
Günter Breithardt, MD
- Department of Cardiology and Angiology, Hospital of the University of Münster, Münster, Germany
- Leibniz Institute for Arteriosclerosis Research, the University of Münster, Münster, Germany
Hans H. Scheld, MD
- Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Münster, Germany
Gabriele Weissen–Plenz, PhD
- Department of Cardiology and Angiology, Hospital of the University of Münster, Münster, Germany
- Leibniz Institute for Arteriosclerosis Research, the University of Münster, Münster, Germany
- Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Münster, Germany
Jürgen R. Sindermann, MD
- Department of Cardiology and Angiology, Hospital of the University of Münster, Münster, Germany
- Leibniz Institute for Arteriosclerosis Research, the University of Münster, Münster, Germany
- Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Münster, Germany
- Address for reprints: Jürgen R. Sindermann, MD, Department of Thoracic and Cardiovascular Surgery, Hospital of the University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany.

Received 16 December 2007; received in revised form 18 February 2008; accepted 20 April 2008. published online 15 August 2008.

Objectives

Cardiac rhabdomyosarcomas are rare, and the pathogenesis of this detrimental disease is widely unknown. Most data are obtained from case reports or small series, and models for systematic pathogenetic studies are lacking. We aimed to establish a transgenic mouse model of cardiac rhabdomyosarcoma formation.

Methods

Standard techniques were used to construct a minigene comprised of the 5′ region of the 1.4-kb SM22α gene (expressed in embryonic cardiac muscle) and the 2.7-kb SV40 T antigen early region. This T antigen fragment includes the coding sequences for the binding sites of p53 and the proteins of the pRb family. Genotyping of transgenic mice was performed by means of polymerase chain reaction, and phenotypic expression was evaluated by means of immunohistochemistry.

Results

Transgenic mice were studied at the age of approximately 8 to 12 weeks. Cardiac tumors were found of variable size in the left or right sides of the heart and were associated with T antigen expression. Histologic analysis revealed a 3.1-fold enhanced cell density, enlarged cell nuclei, and a 3.4-fold enhanced DNA content. Phenotypic characterization of cardiac tumors resulted in positive staining for desmin, smooth muscle α-actin, troponin C, and Myo D1, which met the criteria for rhabdomyosarcomas.

Conclusions

To the best of our knowledge, the present study is the first description of a mouse model of cardiac rhabdomyosarcoma formation based on genetic modulation. Our model will be a valuable tool for illuminating the pathogenesis of cardiac rhabdomyosarcomas and will allow the testing of new therapeutic approaches to fight this dreadful disease.

Abbreviations and Acronyms: FDG, ¹⁸F-Fluordeoxyglucose, PET, positron emission tomography, TAg, tumor antigen

CTSNet classification: 18, 29