Análise de fenótipos de resistência e suscetibilidade ao desenvolvimento de encefalomielite autoimune experimental: Importância do background genético no delineamento experimental de um estudo

Abstract

Despite advances in science and technology in the search for alternative methods to replace animals in research, they are still indispensable for the evolution of scientific research and public health. For the refinement of research in animals, several models and genetic editing techniques were developed, which allow changes in the characteristics or properties of living organisms, generating reliable models of human systems and diseases in animals, contributing to the elucidation of illnesses mechanism and treatment. Experimental models developed through bidirectional genetic selection are valuable tools for the study of gene expression and modulation of multifactorial characters, allowing the concentration of genes of interest to the phenotypic character studied. The Experimental Autoimmune Encephalomyelitis (EAE) model is widely used for a better understanding of the mechanisms involved in the development and progression of Multiple Sclerosis, a currently uncurable disease. This project aims to evaluate the importance of genetic background in the development of EAE, in strains genetically selected for maximum (AIRmax) and minimum (AIRmin) inflammatory response. The results demonstrate that the AIRmax animals are susceptible to the disease, as well as the strain classically used in the literature to develop the EAE model, C57BL/6. The AIRmin animals do not develop any clinical motor alterations, confirming the resistance factor of this strain to the development of EAE. Global genetic analysis showed that signaling pathways related to this disease are inhibited in AIRmin animals. Thus, we can suggest that these pathways play a key role in the development of EAE, and these animals could be used to assess the importance of these pathways and the modulating genes involved in this process. Given the importance of the genetic background for the reduction and refinement of the animals use, we can suggest that the collaborative work between biotherists and researchers can be extremely relevant for a scientific project experimental design.