Transcriptomic Challenges We Faced with Animal Models for Neurological Disorders.

Simulation of a human neurological disease on an animal model has the advantage of allowing control and manipulation of most of the regulating factors and producing real biological replicas while, beyond several common traits, every human is dynamic and unique. Moreover, one can explore novel therapeutic strategies on animals before asking permission to apply them to humans. Nevertheless, experimental outcomes depend on species, strain, sex, age, hormonal status, diet, exposure to hypoxia, toxins, radiation, external stimuli, stress, and housing conditions. Further complications stem from tissue hetero-cellularity, technological constraints, computational complexity and difficulties integrating the experimental results into a coherent biological picture. Moreover, most diseases are multi-factorial and associated with altered structure and/or expression of several genes. A major problem with genetically engineered animals is that together with the targeted gene(s), numerous other genes are mutated and/or regulated, owing to their interlinkage in functional pathways. This experience-based methodological commentary presents the challenges, relevance and limitations of the mouse, rat and rabbit models we used to decipher the transcriptomic alterations associated with several neurological disorders. Links to publicly accessible databases presenting experimental protocols and expression profiles are provided for readers interested in reanalyzing our data and comparing them with others' results.