Table 2.
Animal models of ALS.
| ALS sub-type | Gene mutations | Animal models |
|---|---|---|
| Spontaneous motor neuron degeneration | Wobbler | Mouse—closely resembles hallmarks of clinical ALS, underlying mutation in Vps54 not identified in human ALS (Moser et al., 2013) |
| Neuromuscular degeneration | Mouse—Strong neuromuscular degeneration phenotype, underlying mutation in Ighmbp2 was found in SMA patients (Van Den Bosch, 2011) | |
| Progressive Motor Neuronopathy | Mouse—Hindlimb paralysis and progressive motor axon degeneration, underlying gene product Tbce associated with human hypoparathyroidism retardation dysmorphism (HRD) syndrome (Van Den Bosch, 2011) | |
| Mendelian fALS | SOD1 | Mouse/Rat—Strong ALS-like phenotype in G93A, G37R, G85R, and D90A; variable severity across entity of SOD lines; H4R and G93A do not exert classical ALS; no TDP-43 abnormalities observed in many lines (Carri et al., 2015) Worm—Some of the cellular and molecular hallmarks of clinical ALS phenotypes (Therrien and Parker, 2014) |
| FUS | Mouse/Rat—Some features of clinical ALS (Deng et al., 2014) Fly—recapitulates key features of ALS (Casci and Pandey, 2015) Worm—displays molecular MN degeneration phenotypes resembling ALS/FTLD (Therrien and Parker, 2014) | |
| TDP-43 | Mouse/Rat—represents some features of clinical ALS, wide range of phenotype variation (some lines no MN phenotype), no clear aggregation or loss of nuclear TDP-43 (Chen-Plotkin et al., 2010; Tsao et al., 2012) Zebrafish—recapitulates some hallmarks of ALS, strong MN degeneration, cytoplasmic TDP-43 Fly—recapitulates some ALS aspects, strong MN degeneration documented, cytoplasmic TDP-43 (Casci and Pandey, 2015) Worm—MN degeneration phenotype (Therrien and Parker, 2014) | |
| Atypical and rare mendelian ALS | ALS2/Alsin | Mouse—A very mild, considerably subtle phenotype; no major MN deficits; loss of cerebellar Purkinje cells (Cai et al., 2005) |
| VAP-B | Mouse—VAP-B (P56S) mutants do not show signs of MN degeneration; cytoplasmic TDP-43 accumulations in MN and spinal cord (Van Den Bosch, 2011) | |
| Dynactin P150glued | Mouse—Axonal transport defects; accumulation of cytoskeletal and synaptic vesicle proteins at NMJ, loss of spinal motor neurons, increase of astrogliosis (Van Den Bosch, 2011) | |
| Genetic abnormality in fALS and sALS | C9ORF72 | Mouse—Motor deficits and loss of cortical and cerebellar neurons similar to clinical symptoms of ALS/FLTD; RNA-foci, TDP-43 pathology; astrogliosis (Rohrer et al., 2015) Zebrafish, fly and worm—MN degeneration, more detailed studies awaiting (Therrien and Parker, 2014; Casci and Pandey, 2015) |
A representation of some of the vertebrate and invertebrate models utilized to study the cellular pathology of MND. The left column group’s spontaneous mutations in animal models found to closely resemble MND pathology, Mendelian and atypical forms of ALS associated mutations. In the middle column disease associated genes are listed. The right column summarizes how far ALS-associated phenotypes resemble the designated models.