Adriamycin-Induced Models of VACTERL Association

Abstract

Animal models are of great importance for medical research. They have enabled analysis of the aetiology and pathogenesis of complex congenital malformations and have also led to major advances in the surgical and therapeutic management of these conditions. Animal models allow us to comprehend the morphological and molecular basis of disease and consequently to discover novel approaches for both surgical and medical therapy. The anthracycline antibiotic adriamycin was incidentally found to have teratogenic effects on rats, producing a range of defects remarkably similar to the VACTERL association of congenital anomalies in humans, providing a reproducible animal model of this condition. VACTERL association is a spectrum of birth defects which includes vertebral, anal, cardiovascular, tracheo-oesophageal, renal and limb anomalies. In recent years, adriamycin rodent models of VACTERL have provided valuable insights into the pathogenesis of this complex association, particularly in relation to tracheo-oesophageal malformations. The adriamycin rat model and adriamycin mouse model are now well established in the investigation of the morphology of faulty organogenesis and the regulation of gene expression in tracheo-oesophageal anomalies.