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 alpha-TM, the murine alpha-TM gene was disrupted by homologous recombination. Homozygous alpha-TM null mice are embryonic lethal, dying between 8 and 11.5 days post coitum. Mice that are heterozygous for alpha-TM are viable and reproduce normally. Heterozygous knockout mouse hearts show a 50% reduction in cardiac muscle alpha-TM mRNA, with no compensatory increase in transcript levels by striated muscle beta-TM or TM-30 isoforms. Surprisingly, this reduction in alpha-TM mRNA levels in heterozygous mice is not reflected at the protein level, where normal amounts of striated muscle alpha-TM protein are produced and integrated in the myofibril. Quantification of alpha-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 alpha-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 alpha-TM mice and control mice. The present study suggests that translational regulation plays a major role in the control of TM expression.
journal_name
Circ Resjournal_title
Circulation researchauthors
Rethinasamy P,Muthuchamy M,Hewett T,Boivin G,Wolska BM,Evans C,Solaro RJ,Wieczorek DFdoi
10.1161/01.res.82.1.116subject
Has Abstractpub_date
1998-01-09 00:00:00pages
116-23issue
1eissn
0009-7330issn
1524-4571journal_volume
82pub_type
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