In vivo characterization of human myofibrillar myopathy genes in zebrafish
- Bührdel, J.B., Hirth, S., Keßler, M., Westphal, S., Forster, M., Manta, L., Wiche, G., Schoser, B., Schessl, J., Schröder, R., Clemen, C.S., Eichinger, L., Fürst, D.O., van der Ven, P.F., Rottbauer, W., Just, S.
- Biochemical and Biophysical Research Communications 461(2): 217-23 (Journal)
- Registered Authors
- Bührdel, John, Forster, Monika, Hirth, Sophia, Just, Steffen, Keßler, Mirjam, Rottbauer, Wolfgang, Westphal, Sören
- Cardiac muscle, Myofibrillar Myopathy, Reverse genetics, Skeletal muscle, Zebrafish
- MeSH Terms
- Disease Models, Animal
- Gene Expression Regulation
- Gene Knockdown Techniques
- Genetic Predisposition to Disease
- Heart Failure/genetics
- Heart Failure/pathology
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology
- Myopathies, Structural, Congenital/genetics
- Myopathies, Structural, Congenital/pathology
- 25866181 Full text @ Biochem. Biophys. Res. Commun.
Bührdel, J.B., Hirth, S., Keßler, M., Westphal, S., Forster, M., Manta, L., Wiche, G., Schoser, B., Schessl, J., Schröder, R., Clemen, C.S., Eichinger, L., Fürst, D.O., van der Ven, P.F., Rottbauer, W., Just, S. (2015) In vivo characterization of human myofibrillar myopathy genes in zebrafish. Biochemical and Biophysical Research Communications. 461(2):217-23.
Myofibrillar myopathies (MFM) are progressive diseases of human heart and skeletal muscle with a severe impact on life quality and expectancy of affected patients. Although recently several disease genes for myofibrillar myopathies could be identified, today most genetic causes and particularly the associated mechanisms and signaling events that lead from the mutation to the disease phenotype are still mostly unknown. To assess whether the zebrafish is a suitable model system to validate MFM candidate genes using targeted antisense-mediated knock-down strategies, we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally. Consistently, targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure. Similar to what was shown in MFM patients, MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences. In summary, our results indicate that the zebrafish is a suitable model to functionally and structurally evaluate novel MFM disease genes in vivo.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes