Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Biochem Biophys Res Commun. 2015 May 29;461(2):217-23. doi: 10.1016/j.bbrc.2015.03.149. Epub 2015 Apr 9.

In vivo characterization of human myofibrillar myopathy genes in zebrafish.

Author information

1
Department of Internal Medicine II, University of Ulm, 89081 Ulm, Germany.
2
Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.
3
Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-University, Munich, Germany.
4
Institute of Neuropathology, University Hospital Erlangen, 91054 Erlangen, Germany.
5
Institute for Biochemistry I, University of Cologne, 50931 Köln, Germany.
6
Institute for Cell Biology, University of Bonn, 53121 Bonn, Germany.
7
Department of Internal Medicine II, University of Ulm, 89081 Ulm, Germany. Electronic address: Wolfgang.Rottbauer@uniklinik-ulm.de.
8
Department of Internal Medicine II, University of Ulm, 89081 Ulm, Germany. Electronic address: Steffen.Just@uniklinik-ulm.de.

Abstract

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.

KEYWORDS:

Cardiac muscle; Myofibrillar myopathy; Reverse genetics; Skeletal muscle; Zebrafish

PMID:
25866181
DOI:
10.1016/j.bbrc.2015.03.149
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center