Phenotypical characterization and central nervous system analysis of mutants equilíbrio and mergulhador induced by mutagenic agent n-ethyl-n-nitrosourea

The mutagenic agent N-ethyl-N-nitrosourea (ENU) is widely used to produce new mutations in mice, giving origin to the equilíbrio (eqlb) which has a mutation in the NADPH oxidase 3 (Nox3) gene, chromosome 17 and mergulhador (mlh) in the gene Otopetrin 1 (Otop1), chromosome 5; both mutant strain showed vestibular impairment. Due to the similarity of the vestibular apparatus between human and mouse, the behavioral analysis of the mutant can be a valuable contribution to identify alterations involved in the control of balance and movement. This study aimed to characterize the behavior of eqlb and mlh mutant mice using the following behavioral tests: evaluation of the general activity by direct observation in the open field, motor coordination in the balance beam, elevated plus maze to evaluate the behavior of the anxious type, T-maze and recognition of objects to evaluate memory. In addition, tail suspension test was used to verify depressive like behavior. The results showed that in relation to the BALB/c mice, the mutants eqlb and mlh showed reduction of auricular reflex, surface-righting reflex, touch response, locomotion and rearing frequency. The reduction of the auricular reflex and the touch response pointed to the impairment of the psychomotor system, and the reduction of the surface-righting reflex showed a possible impairment of the psychomotor system. The reduction in the rearing frequency was, probably, a consequence of the motor impairment observed in the mutant strains. The results of the elevated plus maze test indicated that the mutants eqlb and mlh showed motor impairment mainly related to motor coordination. The increased immobility time in the tail suspension test and the inability to swim in eqlb and mlh mice reinforced the role of the vestibular system in maintaining the perception of gravity, movement, and balance. (AU)