title: A bone to pick with zebrafish.
abstract: The development of high-throughput sequencing and genome-wide association studies allows us to deduce the genetic factors underlying diseases much more rapidly than possible through classical genetics, but a true understanding of the molecular mechanisms of these diseases still relies on integrated approaches including in vitro and in vivo model systems. One such model that is particularly suitable for studying bone diseases is the zebrafish (Danio rerio), a small fresh-water teleost that is highly amenable to genetic manipulation and in vivo imaging. Zebrafish physiology and genome organization are in many aspects similar to those of humans, and the skeleton and mineralizing tissues are no exception. In this review, we highlight some of the contributions that have been made through the study of mutant zebrafish that feature bone and/or mineralization disorders homologous to human diseases, including osteogenesis imperfecta, fibrodysplasia ossificans progressiva and generalized arterial calcification of infancy. The genomic and phenotypic similarities between the zebrafish and human cases are illustrated. We show that, despite some systemic physiological differences between mammals and teleosts, and a relative lack of a history as a model for bone research, the zebrafish represents a useful complement to mouse and tissue culture systems in the investigation of genetic bone disorders.
authors.affiliation: Hubrecht Institute-KNAW & University Medical Centre Utrecht , Utrecht, The Netherlands.
authors.forename: Eirinn W
authors.initials: EW
authors.lastname: Mackay
authors.affiliation: Hubrecht Institute-KNAW & University Medical Centre Utrecht , Utrecht, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Apschner
authors.affiliation: Hubrecht Institute-KNAW & University Medical Centre Utrecht , Utrecht, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulte-Merker