Exploring the Behavioral Traits of Male Mutant Crup Mice as an Experimental Neurodegenerative Disease Model

Resumo (EN)

The congenic BALB/c-crup (‘crup’ meaning ‘cruza-pernas’ in Portuguese or cross legs in English), a homozygous recessive mutant mouse derived from N-ethyl-N-nitrosourea mutagenesis, exhibits a unique phenotype characterized by hindlimb crossing when the mouse is suspended by its tail, along with age-related neuromotor issues. The study aimed to identify the genetic mutation causing the BALB/c-crup phenotype and evaluate the behavioral responses of the mice. Open field test, elevated plus maze, and elevated beam experiments were conducted to evaluate general activity, motor function, as well as sensorimotor and autonomic nervous systems. Genetic mapping and exome analysis identified a nonsynonymous (missense mutation), a single nucleotide variant, in the Taf15 gene. This mutation results in the p.G55S substitution, where glycine is replaced by serine at position 55 in the gene product. Longitudinal assessment by the open field test revealed altered locomotion, decreased mobility, and reduced rearing and grooming frequency in mutant mice. Sensorimotor function declines were observed through reduced surface righting reflex scores, grip strength, and increased hindquarter angle. In the elevated beam test, mutants exhibited tail hypotonia and aversion to traversing the beam. The elevated plus maze revealed altered behavior in closed arms, suggesting increased anxiety-like behavior or sensorimotor impairment. Our findings provide insights into neurologic and behavioral anomalies associated with a Taf15 gene mutation. The altered locomotion, sensory impairments, and disorientation observed in the crup phenotype indicate a progressive neuromotor condition, potentially serving as a novel mouse model for neurodegenerative diseases.