Myopathy model's relatively relaxed

Zebrafish mutant embryos provide useful models for several human diseases. Now, Hirata and co-workers identify the relatively relaxed(ryr) mutant as a model for the human congenital myopathy multi-minicore disease (MmD; see p. 2771). MmD is caused by mutations in ryanodine receptor 1 (RYR1; a Ca²⁺-release channel) and characterized by small amorphous cores in muscle fibres. ryr embryos, unlike wild-type embryos, only swim slowly when touched. This phenotype, the researchers show, is caused by impaired excitation-contraction coupling, which prevents strong contractions of the mutant's fast muscles. As in MmD, these muscles have amorphous cores. Furthermore, most of the ryr1b mRNA (which encodes RyR1) in ryr mutants carries a nonsense mutation generated by aberrant splicing; a similar deficit occurs in one type of MmD. Finally, the researchers report, ryr mutant embryos treated with antisense morpholino oligonucleotides that block this aberrant splicing swim normally. A therapeutic strategy based on this approach might, therefore, provide a treatment for some cases of MmD.