Phylogeny can inform animal model development for both inherited and induced conditions: Duchenne Muscular Dystrophy (DMD) and Fetal Alcohol Spectrum Disorders (FASD)

Abstract

Abstract:    The use of animal models in research on human and veterinary diseases and disorders is retracting, though it is likely to remain critical for decades.  In light of increasing regulation and expectations of judicious use of animal subjects, we examine the idea that the use of animal models can be guided by phylogenetic relationships and modern evolutionary and cladistic analyses.  Given that inherited disorders, and indeed, even the developmental and physiological responses to non-inherited conditions, are subject to evolutionary forces, it follows that the observed differences in model organisms are the products of evolutionary divergence.  Understanding that divergence has the potential to elucidate which taxa are most likely to exhibit any given symptom or manifest a reaction in a broadly predictable fashion.  We examine two case studies, one the inherited disorder Duchenne Muscular Dystrophy, and the other an entirely environmentally induced problem, Fetal Alcohol Spectrum Disorder, or Fetal Alcohol Syndrome.  Both case studies reveal symptoms are largely congruent with phylogeny, suggesting relatively conservative evolution of developmental pathways.  It follows that it is possible to characterize the manifestation of symptoms or dysmorphologies to broad phylogenetic groups.  These data can then be used to inform research into possible treatments based on molecular genetic techniques sourced from unaffected taxa or even provide an evolutionary rationale for maximizing ethical decisions in the use and development of animal models in biomedical research.  We argue that the technique should become standard practice in the development of animal models.