Introduction
ALS genes in ALS patients
SOD1
TARDBP
FUS
C9ORF72
Models for ALS
Caenorhabditis elegans and Zebrafish (Danio rerio)
Caenorhabditis elegans and Zebrafish models of SOD1 mutation
Caenorhabditis elegans and Zebrafish models of FUS mutation
Caenorhabditis elegans and Zebrafish models of TDP-43 mutation
Caenorhabditis elegans and Zebrafish models of C9ORF72 mutation
Drosophila melanogaster
Drosophila melanogaster model of SOD1 mutation
Drosophila melanogaster model of FUS mutation
Drosophila melanogaster model of TDP-43 mutation
Drosophila melanogaster model of C9ORF72 mutation
Rodents (mouse and rat)
Gene type (Refs.) | Promoter | Cortical and hippocampal MNL | Cognitive deficit | Gliosis | Paralysis | Mechanism | Cytoplasmic inclusion |
---|---|---|---|---|---|---|---|
Human SOD1 | ND | Yes | Yes | Yes | GOF | SOD1, vac | |
SOD1-A4V [113] | Human SOD1 | No | ND | No | No | ND | None |
SOD1-D90A [112] | Human SOD1 | No | ND | Yes | Yes | GOF | SOD1, vac |
Human SOD | ND | ND | Yes | Yes | GOF | SOD1, UBI, LBHI | |
Human SOD1 | No | ND | Yes | Yes | GOF | SOD1, vac | |
hSOD1WT [15] | Human SOD1 | ND | ND | Yes | Yes | GOF | SOD1, vac |
hSOD1WT [118] | Human SOD1 | ND | ND | Yes | No | GOF | SOD1, vac, UBI |
BAC | ND | Yes | Yes | No | GOF | TDP43, UBI | |
mPrp | ND | ND | Yes | Yes | LOF | UBI | |
TARDBP-M337V [121] | mThy1 | Yes | ND | Yes | Yes | GOF, LOF | TDP43, UBI, Variable |
mPrp | Yes | Yes | ND | No | GOF, LOF | TDP43 | |
mPrp | Yes | ND | ND | No | GOF, LOF | Vac | |
mPrp | Yes | ND | Yes | Yes | GOF | TDP43, p62, vac, UBI | |
BAC | ND | Yes | Yes | No | GOF | TDP43, UBI | |
BAC, mPrp | ND | ND | Yes | Yes | GOF | TDP43, vac, UBI | |
Tau, mPrp | ND | ND | Yes | Yes | GOF, LOF | Diffused FUS | |
CAG | ND | ND | Yes | Yes | GOF, LOF | None | |
FUS-P525L [129] | Tau | ND | ND | Yes | Yes | GOF | Diffused FUS |
Tau, MPrp | No | ND | Yes | Yes | GOF | FUS, UBI | |
HR | Yes(C), ND(H) | ND | ND | No | GOF | FUS | |
BAC | No | No | No | No | ND | DPR, RNA foci | |
BAC | No | No | No | No | ND | DPR), RNA foci | |
AAV-mediated somatogenesis | Yes(C), ND(H) | Yes | Yes | No | GOF | DPR, RNA foci, TDP43 | |
AAV-mediated somatogenesis | Yes(C), ND(H) | Yes | Yes | No | GOF | DPR, RNA foci, TDP43 | |
self-complementary AAV9 | Yes | Yes | No | No | GOF | RNA foci, TDP43 | |
BAC | Yes(C), ND(H) | Yes | No | No | GOF | DPR), RNA foci | |
BAC | Yes | Yes | Yes | Yes | GOF | DPR, RNA foci, TDP43 |
Rodent models of SOD1 mutation
Rodent models of TDP-43 mutation
Rodent models of FUS mutation
Rodent models of C9ORF72 mutation
Canine models
Swine models
Non-human primate models
Species [Refs.] | Genetic anomaly | Modification approach | Pathology and phenotypes |
---|---|---|---|
TDP-43 (M337V) | Brain regional expression of transgenic TDP-43 | Cytoplasmic accumulation of mutant TDP-43, motor function deficits | |
Monkey [210] | TDP-43 (WT) | Spinal cord expression of human WT TDP-43 | Progressive motor weakness and muscle atrophy. Cytoplasmic mislocalization of TDP-43 |
SOD1 | Intrathecal delivery of AAV encoding SOD1-specific microRNA | Not described | |
Monkey [213] | FUS | Injection of FUS-targeted shRNA | Not described |
Pig [204] | TDP-43 (M337V) | Embryonic expression of transgenic TDP-43 | Severe phenotypes and early death |
Pig [202] | hSOD1 (G93A) | Embryonic expression of transgenic SOD1 | Hind limb movement deficits, loss of motor neurons, formation of neuronal intranuclear inclusions in early disease stage |
Pig [201] | hSOD1 (G93A) | Embryonic expression of transgenic SOD1 | No ALS-like phenotypes |
SOD1 (T18S, E40K) | Spontaneous | Progressive axonal degeneration, muscle atrophy, and SOD1 inclusions |