QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 27 June 2007
doi: 10.1242/dev.004531

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.004531v1 134/15/2771    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hirata, H. Articles by Kuwada, J. Y. Search for Related Content PubMed PubMed Citation Articles by Hirata, H. Articles by Kuwada, J. Y.

Zebrafish relatively relaxed mutants have a ryanodine receptor defect, show slow swimming and provide a model of multi-minicore disease

Hiromi Hirata^1,2,, Takaki Watanabe¹, Jun Hatakeyama³, Shawn M. Sprague², Louis Saint-Amant^2,*, Ayako Nagashima², Wilson W. Cui², Weibin Zhou² and John Y. Kuwada²

¹ Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.
² Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
³ Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.

Author for correspondence (e-mail: hhirata{at}bio.nagoya-u.ac.jp)

Accepted 29 May 2007

Wild-type zebrafish embryos swim away in response to tactile stimulation. By contrast, relatively relaxed mutants swim slowly due to weak contractions of trunk muscles. Electrophysiological recordings from muscle showed that output from the CNS was normal in mutants, suggesting a defect in the muscle. Calcium imaging revealed that Ca²⁺ transients were reduced in mutant fast muscle. Immunostaining demonstrated that ryanodine and dihydropyridine receptors, which are responsible for Ca²⁺ release following membrane depolarization, were severely reduced at transverse-tubule/sarcoplasmic reticulum junctions in mutant fast muscle. Thus, slow swimming is caused by weak muscle contractions due to impaired excitation-contraction coupling. Indeed, most of the ryanodine receptor 1b (ryr1b) mRNA in mutants carried a nonsense mutation that was generated by aberrant splicing due to a DNA insertion in an intron of the ryr1b gene, leading to a hypomorphic condition in relatively relaxed mutants. RYR1 mutations in humans lead to a congenital myopathy, multi-minicore disease (MmD), which is defined by amorphous cores in muscle. Electron micrographs showed minicore structures in mutant fast muscles. Furthermore, following the introduction of antisense morpholino oligonucleotides that restored the normal splicing of ryr1b, swimming was recovered in mutants. These findings suggest that zebrafish relatively relaxed mutants may be useful for understanding the development and physiology of MmD.

Key words: Zebrafish, Ryanodine receptor, Muscle, Calcium, Multi-minicore disease

Related articles in Development:

Myopathy model's relatively relaxed

Development 2007 134: e1502. [Full Text]  

This article has been cited by other articles:

				M. J. Jurynec, R. Xia, J. J. Mackrill, D. Gunther, T. Crawford, K. M. Flanigan, J. J. Abramson, M. T. Howard, and D. J. Grunwald Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle PNAS, August 26, 2008; 105(34): 12485 - 12490. [Abstract] [Full Text] [PDF]

				L. Xu, Y. Wang, N. Yamaguchi, D. A. Pasek, and G. Meissner Single Channel Properties of Heterotetrameric Mutant RyR1 Ion Channels Linked to Core Myopathies J. Biol. Chem., March 7, 2008; 283(10): 6321 - 6329. [Abstract] [Full Text] [PDF]