Molecular Pathways and Animal Models of d-Transposition of the Great Arteries

During normal cardiovascular development, the outflow tract becomes septated and rotates so that the separate aorta and pulmonary trunk are correctly aligned with the left and right ventricles, respectively. However, when this process goes wrong, the aorta and pulmonary trunk are incorrectly positioned, resulting in oxygenated blood being directly returned to the lungs, with deoxygenated blood being delivered to the systemic circulation. This is termed transposition of the great arteries (TGA). The precise etiology of TGA is not known, but the use of animal models has elucidated that genes involved in determination of the left– embryonic body axis play key roles. Other factors such as retinoic acid levels are also crucial. This chapter reviews the animal models presenting with TGA that have been generated by genetic manipulation or with exogenous agents.