Molecular and physiological effects of α-tropomyosin ablation in the mouse

Prabhakar Rethinasamy, Mariappan Muthuchamy, Tim Hewett, Greg Boivin, Beata M. Wolska, Christian Evans, R. John Solaro, David F. Wieczorek

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Tropomyosin (TM) is an integral component of the thin filament in muscle fibers and is involved in regulating actin-myosin interactions. TM is encoded by a family of four alternatively spliced genes that display highly conserved nucleotide and amino acid sequences. To assess the functional and developmental significance of α-TM, the murine α-TM gene was disrupted by homologous recombination. Homozygous α-TM null mice are embryonic lethal, dying between 8 and 11.5 days post coitum. Mice that are heterozygous for α- TM are viable and reproduce normally. Heterozygous knockout mouse hearts show a 50% reduction in cardiac muscle α-TM mRNA, with no compensatory increase in transcript levels by striated muscle β-TM or TM-30 isoforms. Surprisingly, this reduction in α-TM mRNA levels in heterozygous mice is not reflected at the protein level, where normal amounts of striated muscle α- TM protein are produced and integrated in the myofibril. Quantification of α-TM mRNA bound in polysomal fractions reveals that both wild-type and heterozygous knockout animals have similar levels. These data suggest that a change in steady-state level of α-TM mRNA does not affect the relative amount of mRNA translated and amount of protein synthesized. Physiological analyses of myocardial and myofilament function show no differences between heterozygous α-TM mice and control mice. The present study suggests that translational regulation plays a major role in the control of TM expression.

Original languageEnglish (US)
Pages (from-to)116-123
Number of pages8
JournalCirculation research
Volume82
Issue number1
DOIs
StatePublished - 1998

Keywords

  • Knockout mouse
  • Translational regulation
  • Tropomyosin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Rethinasamy, P., Muthuchamy, M., Hewett, T., Boivin, G., Wolska, B. M., Evans, C., Solaro, R. J., & Wieczorek, D. F. (1998). Molecular and physiological effects of α-tropomyosin ablation in the mouse. Circulation research, 82(1), 116-123. https://doi.org/10.1161/01.RES.82.1.116