Authors
Hannah Cole
Summary
Amyotrophic Lateral Sclerosis (ALS) is a late adult-onset, quickly progressing paralytic disorder marked by selective degeneration of motor neurons in the motor cortex and spinal cord. For ALS patients, this disease leads to paralysis and eventual death. ALS patients are classified into two main categories, sporadic (sALS) and familial (fALS). Both fALS and sALS patients present with muscle weakness and atrophy, as well as spasticity due to the loss of both upper and lower motor neurons.
Introduction
A rather large subset (~20%) of fALS cases have been linked to mutations in the Cu/Zn superoxide dismutase 1 gene (SOD1). Earliest models used toxic levels or deficiencies of metals such as lead or mercury as a way to study the disease. Genetic mutations in superoxide dis-mutase 1 (SOD1), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and transactivation response (TAR) DNA-binding protein with molecular weight 43 kDa (TDP - 43) genes have been identified in 25–35% of the fALS cases. Due to numerous possible etiologies of sALS, most of the current research models focus on genetic etiologies. Still, the majority of early research was performed using observational or spontaneous cases of ALS in both humans and animals, until technology and knowledge allowed more complex models with genetic manipulation.
Acroscell fully understands advantages and limitations between each kind of animal models for investigating ALS. It is essential for your research to find the best matching animal model at the beginning. We will work side-by-side with you to decide the most appropriate model for your specific experimental hypotheses.
Materials
Current research into neurodegenerative disorders relies heavily on animal models that recapitulate human disease. A large number of animal models are toxin-based, utilizing chemicals or metals that have been correlated with human disease. As a whole, current animal models serve as adequate substitutes to their human counterparts, providing valuable tools for translational and basic science research in ALS, with the caveat that most models typically do not recapitulate the totality of the human disease.
For many years, the gold standard for modeling fALS has been murine models of human SOD1 mutations; however, more recent models have been developed which may better recapitulate different aspects of ALS disease progression. Nevertheless, even current models may not fully mimic all facets of disease etiology, progression, or pathology, necessitating continued research into developing models that more closely replicate the clinical manifestations of the disease.
References
Acevedo-Arozena A, et al. A comprehensive assessment of the SOD1G93A low-copy transgenic mouse, which models human amyotrophic lateral sclerosis. Dis Model Mech. 2011; 4: 686–700.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 242
- Comments 0