Sage Journals: Discover world-class research

Abstract

Transgenic mice expressing atrial natriuretic factor-SV40 T-antigen fusion genes (ANF-TAG) developed cardiac tumors asymmetrically in the right atrium. Features associated with cardiac failure, including increased plasma creatine kinase activity (MM and MB) and ventricular dysrhythmias, also were associated with atrial tumor growth. These atrial tumors were able to grow at histocompatible sites (subcutaneously in syngeneic animals) for protracted periods of time yielding a series of transplantable atrial tumor lineages. The transplantable tumors displayed several cardiac-specific characteristics, such as endogenous electrical activity and expression of cardiac-specific proteins. These transplantable atrial tumors constitute a novel experimental resource for developing cell lines which display an adult cardiac phenotype.

Keywords

Heart growth proliferation transformation muscle cancer

References

Bligh

and Dyer

(1959). A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37: 911–917.

Brinster

and Palmiter

(1986). Introduction of genes into the germline of animals. The Harvey Lectures 1–38.

Cory

and Adams

(1988). Transgenic mice and oncogenesis. Ann. Rev. Immunol. 6: 25–48.

Claycomb

and Lanson

Jr (1984). Isolation and culture of the terminally differentiated adult mammalian cardiac muscle cell. In Vitro 20: 647–651.

Davis

, Weintraub

, and Lassar

(1987). Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51: 987–1000.

Deguchi

, Zuma

, Mamaguchi

, Kurimoto

, Sawamura

, Awata

, Kishimoto

, and Onishi

(1988). Cellular oncogene expression in the idiopathic cardiomyopathic hamster heart during the growing process. J. Mol. Cell Cardiol. 20: 801–809.

Delcarpio

, Claycomb

, and Moses

(1989). Ultrastructural morphometric analysis of cultured neonatal and adult rat ventrical cardiac muscle cells. Am. J. Anat. 186: 335–345.

Field

(1988). Atrial natriuretic facror-sv40 T antigen transgenes produce tumors and cardiac arrhythmias in mice. Science 239: 1029–1033.

Gordon

and Ruddle

(1983). Gene transfer into mouse embryos: Production of transgenic mice by pronuclear injection. Methods Enzymol. 101C: 411–433.

10.

Harlow

and Lane

(1989). Antibodies, A Laboratory Manual. Cold Spring Harbor Laboratory Press, New York.

11.

Hogan

, Costantini

, and Lacy

(1986). Manipulating the Mouse Embryo—A Laboratory Manual. Cold Spring Harbor Laboratory Press, New York.

12.

Icardo

(1988). Cardiac morphogenesis and development. Experientia 44: 909–1032.

13.

Knudson

Jr (1977). Genetic predisposition to cancer. In: Origins of Human Cancer. Hiatt

, Watson

, and Winsten

(eds). Cold Spring Harbor Laboratory, New York, pp. 45–52.

14.

Land

, Parada

, and Weinberg

(1983). Cellular oncogenes and multistep carcinogenesis. Science 222: 771–778.

15.

Palmiter

and Brinster

(1986). Germline transformation of mice. Ann. Rev. Genetics 20: 465–499.

16.

Sambrook

, Fritsch

, and Maniatis

(1989). Molecular Cloning: A Laboratory Manual, 2nd ed. Cold Spring Harbor Press, New York.

17.

Steinhelper

and Field

(1990). SV40 large T-antigen induces cardiocyte proliferation in transgenic mice. In: The Development and Regenerative Potential of Cardiac Muscle, Oberpriller

(ed). Harwood Academic Press, New York.

18.

Steinhelper

, Cochrane

, and Field

(1990). Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes. Hypertension 16: 301–307.

19.

Steinhelper

, Lanson

Jr , Dresdner

, Delcarpio

, Wit

, Claycomb

, and Field

(1990). Proliferation in vivo and in culture of differentiated adult atrial cardiomyocytes from transgenic mice. Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H1826–H1834.

20.

Thomas

(1980). Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. USA 77: 5201–5205.

Cardiac Tumors and Dysrhythmias in Transgenic Mice 1

Abstract

Keywords

References