Modeling human muscle disease in zebrafish

Abstract

Zebrafish reproduce in large quantities, grow rapidly, and are transparent early in development. For these reasons, zebrafish have been used extensively to model vertebrate development and disease. Like mammals, zebrafish express dystrophin and many of its associated proteins early in development and these proteins have been shown to be vital for zebrafish muscle stability. In dystrophin-null zebrafish, muscle degeneration becomes apparent as early as 3 days post-fertilization (dpf) making the zebrafish an excellent organism for large-scale screens to identify other genes involved in the disease process or drugs capable of correcting the disease phenotype. Being transparent, developing zebrafish are also an ideal experimental model for monitoring the fate of labeled transplanted cells. Although zebrafish dystrophy models are not meant to replace existing mammalian models of disease, experiments requiring large numbers of animals may be best performed in zebrafish. Results garnered from using this model could lead to a better understanding of the pathogenesis of the muscular dystrophies and the development of future therapies.

The zebrafish dystrophic mutantsoftymaintains muscle fibre viability despite basement membrane rupture and muscle detachment

“…None of these diseases are currently curable, and many experimental therapies are being investigated. A viable zebrafish muscular dystrophy model has the potential to make a significant contribution to research in this field Guyon et al, 2007). Uncovering the mechanisms that enable the sof mutant to recover from severe, early muscle degeneration and thrive as adults may ultimately have important ramifications.…”

Technologies and Analyses Using Medaka to Evaluate Effects of Space on Health

“…Medaka and zebrafish, with their transparent bodies through the development, have made contributions to clarifying the molecular mechanism in vertebrate morphogenesis such as whole nuclei tracing during gastrulation (Keller et al, 2008;Ma and Raible, 2009). Recently, small fish are being used as a disease model for infection and immune systems, the heart or liver diseases, muscular dystrophies, or even in the individual learning study (Wittbrodt et al, 2002;Furutani-Seiki and Wittbrodt, 2004;Guyon et al, 2007;Okamoto et al, 2008;Martin and Renshaw, 2009;Rocke et al, 2009).…”

Muscle stem cells and model systems for their investigation

“…A DMD-affected organism rapidly exhausts its satellite cell reserves owing to the continual cell cycles, and thereby loses its regenerative capacity (Webster and Blau, 1990). Many researchers have turned to animal models to elucidate the mechanisms leading to muscular diseases; the species used include the dog, cat, mouse, zebrafish, and invertebrates, in which all developmental stages of the disease can be easily assessed (Watchko et al, 2002;Guyon et al, 2007). Most experiments have been performed on the mdx mouse, which has no functional dystrophin in its muscles.…”