Tropomodulin expression in developing hearts of normal and cardiac mutant Mexican axolotl

In the axolotl, Ambystoma mexicanum, a simple, recessive cardiac-lethal mutation in gene "c" results in the hearts of c/c homozygous animals being deficient in sarcomeric tropomyosin (TM) and failing to form mature myofibrils. Subsequently, the mutant hearts do not beat. A three-step model...

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Published inCardiovascular toxicology Vol. 6; no. 2; pp. 85 - 98
Main Authors McLean, Matthew D, Zajdel, Robert W, Dube, Syamalima, Thurston, Harold, Dube, Dipak K
Format Journal Article
LanguageEnglish
Published United States Springer Nature B.V 2006
Subjects
Ambystoma
Animals
Antibodies, Monoclonal
Biomarkers
Blotting, Western
Erythrocytes - metabolism
Genes, Lethal - genetics
Heart - growth & development
Immunohistochemistry
Microscopy, Confocal
Mutation - physiology
Myocardium - metabolism
Myofibrils - pathology
Myofibrils - physiology
Tropomodulin - biosynthesis
Tropomodulin - deficiency
Tropomodulin - genetics
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Summary:In the axolotl, Ambystoma mexicanum, a simple, recessive cardiac-lethal mutation in gene "c" results in the hearts of c/c homozygous animals being deficient in sarcomeric tropomyosin (TM) and failing to form mature myofibrils. Subsequently, the mutant hearts do not beat. A three-step model of myofibril assembly recently developed in cell culture prompted a reassessment of the myofibril assembly process in mutant hearts using a relatively new late marker for thin filament assembly, tropomodulin (Tmod). This is, to the best of our knowledge, the first report of tropomodulin in an amphibian system. Tropomodulin antibodies were immunolocalized to the ends of the thin filaments. Tropomodulin was also found in discrete punctate spots in normal and mutant hearts, often in linear arrays suggestive of early myofibril formation. The tropomodulin spots assessed in stage 41/42 mutant hearts co-localized with antibodies to other myofibrillar proteins indicative of nascent myofibril formation. This suggests a failure of elongation/maturation of nascent myofibrils, which could be a consequence of decreased TM levels or increased Tmod/ TM ratio. Unlike tropomyosin, there is no apparent decrease in the level of Tmod expression in mutant hearts.
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ISSN:1530-7905
1530-7905
1559-0259
DOI:10.1385/CT:6:2:85