Abstract
Transgenic animals provide a model system to elucidate the role of specific proteins in development. This model is now being used increasingly in the cardiovascular system to study cardiac growth and differentiation. During cardiac myocyte development a transition occurs from hyperplastic to hypertrophic growth. In the heart the switch from myocyte proliferation to terminal differentiation is synchronous with a decrease in c-myc mRNA abundance. To determine whether c-myc functions to regulate myocyte proliferation and/or differentiation, we examined the in vivo effect of increasing c-myc expression during fetal development and of preventing the decrease in c-myc mRNA expression that normally occurs during myocyte development. The model system used was a strain of transgenic mice exhibiting constitutive expression of c-myc mRNA in cardiac myocytes throughout development. Increased c-myc mRNA expression is associated with both atrial and ventricular enlargement in the transgenic mice. This increase in cardiac mass is secondary to myocyte hyperplasia, with the transgenic hearts containing greater than twice as many myocytes as nontransgenic hearts. The results of this study indicate that constitutive expression of c-myc mRNA in the heart during development results in enhanced hyperplastic growth, and suggest a regulatory role for the c-myc protooncogene in cardiac myogenesis
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References
Bugaisky L, Zak R: Biological mechanisms of hypertrophy. In: H Fozzard, E Haber, R Jennings, A Katz, H Morgan (eds) The Heart and Cardiovascular System-Scientific Foundations. Raven Press, New York, 1986, pp 1491–1506
Marcu KB: Regulation of expression of the c-myc pro-tooncogene. Bioessays 6: 28–32, 1987
Ramsay GM, Moscovici G, Moscovici C, Bishop JM: Ne-oplastic transformation and tumorigenesis by the human protooncogene MYC. Proc Natl Acad Sci USA 87: 2102–2106, 1990
Endo T, Nadal-Ginard B: Transcriptional and posttran-scriptional control of c-myc during myogenesis: its mRNA remains inducible in differentiated cells and does not suppress the differentiated phenotype. Mol Cell Biol 6: 1412–1421, 1986
Sejersen T, Sumegi J, Ringertz NR: Density-dependent arrest of DNA replication is accompanied by decreased levels of c-myc mRNA in myogenic but not in differentiation-defective myoblasts. J Cell Physiol 125: 465–470, 1985
Denis N, Blanc S, Leibovitch MP, Nicolaiew N, Dautry F, Raymondjean M, Kruh J, Kitzia A: c-Myc oncogene ex-pression inhibits the initiation of myogenic differentiation. Exper Cell Res 172: 212–217, 1987
Schneider MD, Perryman MB, Payne PA, Spizz G, Roberts R, Olson E: Autonomous expression of c-myc in BC3H1 cells partially inhibits but does not prevent myogenic differentiation. Mol Cell Biol 7: 1973–1977, 1987
Schneider MD, Payne PA, Ueno H, Perryman MB, Roberts R: Dissociated expression of c-myc and a fas-related competence gene during cardiac myogenesis. Mol Cell Biol 6: 4140–4143, 1
Swain JL, Stewart TA, Leder P: Parental legacy determines methylation and expression of an autosomal transgene: A molecular mechanism for parental imprinting. Cell 50: 719–727, 1987
Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294–5299, 1979
Simpson P, Savion S: Differentiation of rat myocytes in single cell culture with and without proliferating nonmyo-cardial cells: Cross-striations, ultrastructure, and chrono-tropic response to isoproterenol. Circ Res 50: 101–116, 1982
Bishop SP, Drummond JL: Surface morphology and cell size measurement of isolated rat cardiac myocytes. J Mol Cell Cardiol 11: 423–433, 1979
Clubb FJ, Bell PD, Kriseman JD, Bishop SP: Myocardial cell growth and blood pressure development in neonatal spontaneously hypertensive rats. Lab Invest 56: 189–197, 1987
Nash GB, Tatham PER, Powell T, Twist VW, Speller RD, Loverock LT: Size measurements on isolated rat heart cells using Couldter analysis and light scatter flow cytometry. Biochem Biophys Acta 587: 99–111, 1979
Gerdes AM, Kriseman JD, Bishop SP: Changes in myocardial cell size and number during the development and reversal of hyperthyroidism in neonatal rats. Lab Invest 48: 598–602, 1983
Izumo S, Nadal-Ginard B, Mahdavi V: Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA 85: 339–343, 1988
Starksen NF, Simpson PC, Bishopric N, Coughlin SR, Lee WM, Escobedo JA, Williams LT: Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Proc Natl Acad Sci USA 83: 8348–8350, 1986
Jackson T, Allard M, Sreenan C, Doss L, Bishop S, Swain JL: The c-myc protooncogene regulates cardiac development in transgenic mice. Molec Cell Biol 10: 3709–3716, 1990
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© 1991 Springer Science+Business Media Dordrecht
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Jackson, T., Allard, M.F., Sreenan, C.M., Doss, L.K., Bishop, S.P., Swain, J.L. (1991). Transgenic animals as a tool for studying the effect of the c-myc proto-oncogene on cardiac development. In: Morgan, H.E. (eds) Molecular Mechanisms of Cellular Growth. Developments in Molecular and Cellular Biochemistry, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3886-8_2
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DOI: https://doi.org/10.1007/978-1-4615-3886-8_2
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