The curveback guppy as a model for human idiopathic-type spinal curvature

Idiopathic (meaning no known cause) scoliosis accounts for 80% of all cases of human spinal curvature, affecting an average of 3%-4% of the global paediatric population. Phenotypic variability, curve pathogenesis that coincides with growth, and the lack of an animal model that does not rely on induced curvature, have made it difficult to discover the etiopathogenesis of this complex deformity. Although a genetic basis is accepted, the specific genes, the mode of inheritance, and the proportion of phenotypic variation due to genetics are not known. Furthermore, factors that explain a propensity for curve severity have not been determined. The discovery of causative and progressive factors would be greatly facilitated by a genetic animal model. With complex human syndromes that involve interactions among genetic, physiological, and environmental forces, an important experimental approach is to first identify genes and biochemical factors in a model animal with a similar phenotype. The curveback mutant guppy [Poecilia reticulata] is the first animal model with heritable morphological and developmental similarities to human idiopathic scoliosis. This thesis describes construction of the curveback lineage and characterization of the curveback phenotype so that it can be applied as model for the discovery and exploration of biological processes that contribute to idiopathic spinal curvature. In addition, I describe our initial efforts for mapping genes that are associated with the curveback deformity. Identification of genes associated with idiopathic-type scoliosis in curveback could help to identify biological processes that are involved in the human deformity, which would lead to methods of effective screening for early curve detection as well as possible therapeutics.