Animal models of human genetic diseases: do they need to be faithful to be useful?

Abstract

With the advances in molecular genetics, animal models of human diseases are becoming more numerous and more refined every year. Despite this, one must recognize that they generally do not faithfully and comprehensively mimic the homologous human disease. Faced with these imperfections, some geneticists believe that these models are of little value, while for others, on the contrary, they are important tools. We agree with this second statement, and in this review, we examine the reasons that may explain the observed differences and suggest means to circumvent or even exploit them. Our opinion is that animal models should be regarded more as tools capable of answering specific questions rather than mere replicas, at a smaller scale, of a given human disease. Far from disappointing they are probably called for a promising future.

Genome-Wide Association Study (GWAS) for Growth Rate and Age at Sexual Maturation in Atlantic Salmon (Salmo salar)

“…In addition to QTL found on Ssa28, previous studies have described QTL on Ssa01 and its equivalent in other salmonid species. For instance, a QTL for age at sexual maturation in Arctic charr was described in linkage group AC-9, that shares homology with Ssa01 [32] and also a QTL for condition factor [24]. In the case of Ssa21, we recently described QTL for grilsing located in the same chromosome; however, in this analysis the QTL was detected for late maturation, which suggests that these regions controlling sexual development contain genes that are involved in both processes.…”

“…Consequently, most identified QTL span a large chromosomal region, from which the identification of a causative gene(s) is problematic. Several studies have described QTL associated with growth and/or sexual maturation in salmonid species including Atlantic salmon [21–25], rainbow trout [26–29], coho salmon [30,31] and Arctic charr [24,32]. Yet, information regarding candidate genes located in these QTL regions is scarce for most species.…”

Proteomics reveals drastic increase of extracellular matrix proteins collagen and dermatopontin in the aged mdx diaphragm model of Duchenne muscular dystrophy

“…Naturally occurring or genetically engineered model systems are widely used for studying fundamental aspects of molecular and cellular pathogenesis, as well as the evaluation of novel therapeutic approaches (33). Ideally, an animal model of a genetic disorder should: i) exhibit similar primary abnormalities and secondary downstream alterations as seen in the corresponding human disease; ii) closely develop most of the multifactorial features observed in complex human pathologies; iii) resemble the pathogenesis of the human disease in onset, progression and severity; iv) show sufficient similarities to human metabolism, physiology and immune responses so that these biological factors do not have a major differentiating influence on disease progression in animal models vs. patients; v) is easy to breed and house at a reasonable cost; vi) be suitable for genetic manipulations and the facilitation of physiological and surgical procedures; and vii) be large enough to yield sufficient amounts of tissue specimens for extended biological analyses (34). Since an important bioethical objection with respect to the humane and responsible use of animal models in biomedical research is often associated with the usage of larger animals, small rodents are the most frequently used alternatives as genetic model systems.…”

Application of Fluorescence Two-Dimensional Difference In-Gel Electrophoresis as a Proteomic Biomarker Discovery Tool in Muscular Dystrophy Research

“…Animal models of human diseases are widely used in the initial identification of novel biomolecules involved in tissue degeneration [39]. In the field of experimental muscle pathology, a large number of animal genocopies are available to study the basic mechanisms of major neuromuscular diseases [40].…”