Sustained cardiomyocyte DNA synthesis in whole embryo cultures lacking the TSC2 gene product

Laura Pajak, Fang Jin, Guang Hui Xiao, Mark Soonpaa, Loren Field, Raymond S. Yeung

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Tuberous sclerosis complex (TSC) is characterized by the appearance of nonmalignant tumors that affect a wide spectrum of organs, including the heart. TSC disease-causing genes have been identified on chromosomes 9 (TSC1) and 16 (TSC2). This study examined the impact of the TSC2 gene product on cardiomyocyte proliferation and terminal differentiation. We took advantage of the observation that Eker rats carry a germ-line TSC2 mutation. Rats heterozygous for the mutation (TSC2(EK/+)) are predisposed to renal carcinoma, whereas animals homosygous for the mutation (TSC2(EK/EK)) die in utero during midgestation. Spontaneously contractile cardiomyocytes were observed after multiple passages of whole embryo cultures prepared from embryonic day 12.5 TSC2(EK/EK) fetuses but not from TSC2(EK/+) or wild-type fetuses. The TSC2(EK/EK) cardiomyocytes continued to actively synthesize DNA after as many as eight passages. Cytological, ultrastructural, and molecular analyses indicated that the TSC2(EK/EK) cardiomyocytes retained a highly differentiated phenotype similar to that observed for normal rat cardiomyocytes during late embryonic and early neonatal life. These results suggested that the TSC2 gene product is required for normal cardiomyocyte cell-cycle withdrawal and terminal differentiation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume273
Issue number3 42-3
StatePublished - Oct 13 1997

Fingerprint

Cardiac Myocytes
Embryonic Structures
DNA
Genes
Tuberous Sclerosis
Fetus
Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 9
Mutation
Germ-Line Mutation
Cell Cycle
Carcinoma
Phenotype
Kidney
Neoplasms

Keywords

  • Antioncogenes
  • Cardiac regeneration
  • Cardiac tumor
  • Eker rat
  • Terminal differentiation
  • Tuberin
  • Tumor suppressors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Sustained cardiomyocyte DNA synthesis in whole embryo cultures lacking the TSC2 gene product. / Pajak, Laura; Jin, Fang; Xiao, Guang Hui; Soonpaa, Mark; Field, Loren; Yeung, Raymond S.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 273, No. 3 42-3, 13.10.1997.

Research output: Contribution to journalArticle

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