Homozygous mice with mutant protein FUS[1-359] overexpression: Innovative possibilities for ALS treatment

Introduction: This study investigates a mouse model with overexpression of the mutant FUS[1-359] protein, which can be used to evaluate the effectiveness of gene therapy and other pharmacological interventions for amyotrophic lateral sclerosis (ALS). The model enhances the deeper understanding of the mechanisms underlying disease progression and allows for testing new therapeutic strategies. Materials and Methods: The study utilized tg_hFUS[1-359] animal lines with a transgenic cassette expressing the human mutant FUS[1-359] protein. Animal groups were formed by crossing hemizygous individuals, and analyses were conducted on lifespan, age of disease manifestation, as well as relative copy number and expression levels of the transgenic cassette. Results and Discussion: The results demonstrated statistically significant differences in the age of onset of initial disease symptoms between homozygous and hemizygous mice. Differences in the copy number of the transgenic insertion were also identified, revealing that homozygous animals exhibited increased expression of the mutant FUS protein in various structures of the central nervous system, consistent with existing literature on ALS pathogenesis. Conclusion: Mice with hyperexpression of the mutant FUS[1-359] protein represent a promising genetic model for evaluating therapeutic approaches to ALS treatment. This model exhibits clear phenotypic manifestations of the disease and can be utilized for investigating gene therapy methods.