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

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

Research output: Contribution to journalArticle

85 Citations (Scopus)

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
StatePublished - 1998
Externally publishedYes

Fingerprint

Tropomyosin
Messenger RNA
Striated Muscle
Myofibrils
Recombinant DNA
Muscle Proteins
Homologous Recombination
Myosins
Knockout Mice

Keywords

  • Knockout mouse
  • Translational regulation
  • Tropomyosin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Rethinasamy, P., Muthuchamy, M., Hewett, T., Boivin, G., Wolska, B. M., Evans, C., ... Wieczorek, D. F. (1998). Molecular and physiological effects of α-tropomyosin ablation in the mouse. Circulation Research, 82(1), 116-123.

Molecular and physiological effects of α-tropomyosin ablation in the mouse. / Rethinasamy, Prabhakar; Muthuchamy, Mariappan; Hewett, Timothy; Boivin, Greg; Wolska, Beata M.; Evans, Christian; Solaro, R. John; Wieczorek, David F.

In: Circulation Research, Vol. 82, No. 1, 1998, p. 116-123.

Research output: Contribution to journalArticle

Rethinasamy, P, Muthuchamy, M, Hewett, T, Boivin, G, Wolska, BM, Evans, C, Solaro, RJ & Wieczorek, DF 1998, 'Molecular and physiological effects of α-tropomyosin ablation in the mouse', Circulation Research, vol. 82, no. 1, pp. 116-123.
Rethinasamy P, Muthuchamy M, Hewett T, Boivin G, Wolska BM, Evans C et al. Molecular and physiological effects of α-tropomyosin ablation in the mouse. Circulation Research. 1998;82(1):116-123.
Rethinasamy, Prabhakar ; Muthuchamy, Mariappan ; Hewett, Timothy ; Boivin, Greg ; Wolska, Beata M. ; Evans, Christian ; Solaro, R. John ; Wieczorek, David F. / Molecular and physiological effects of α-tropomyosin ablation in the mouse. In: Circulation Research. 1998 ; Vol. 82, No. 1. pp. 116-123.
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