Table 2. Selected mouse models of neurodegenerative diseases.
| Model Name | Disease Applicability | Expressed Protein (Mutation) | Promotor | Pathological Features | Limitations |
|---|---|---|---|---|---|
| APPswe/PS1dE9143 | AD | APP (KM594/5NL), presenilin 1 (deletion of exon 9) | Mouse prion protein | Aβ plaques in cortex and hippocampus by 4mo144 | No NFTs, no neuronal death |
| Tg2576145 | AD | APP (K670/671L) | Hamster prion protein | Aβ plaques after 12mo146 | No NFTs, no neuronal death |
| 3xTg147 | AD | APP (K670/671L), presenilin 1 (M146V), tau (P301L) | Mouse Psen1 (presenilin 1), Mouse Thy1 (APP, tau) | Aβ plaques by 6mo, hippocampal then neocortical NFTs appear between 12-18mo | NFT formation may be independent of Aβ148 |
| rTg4510149 | AD, FTD | tau (P301L)* | Mouse prion protein (tau), mouse calmodulin-kinase II (transactivator) | Hippocampal NFTs and neuronal death by 4mo, cortical NFTS by 4mo150 | AD: no Aβ pathology FTD: Greatest NFT and neuronal death in hippocampus |
| Thy1-TDP-43151 | FTD, ALS | Human TDP-43 (wild-type over expressed) | Mouse Thy1 | Nuclear and cytoplasmic (ubiquitinated, phosphorylated) inclusions primarily in motor cortex and hippocampus by 6mo, neuronal death by 6mo | Subcellular localization of TDP-43 is not reported |
| Prnp-FUS152 | ALS | Human FUS (wild-type) | Mouse prion protein | Non-ubiquitinated inclusions in the motor and somatosensory cortices and spinal cord, 60% motor neuron death in spinal cord by 11 weeks old | No neuronal loss and little microglial or astrocytic response in brain |
| SOD1-G93A153 | ALS | SOD1 (G93A) | Endogenous human SOD1 promoter | 55% reduction in spinal cord neuron count by 123 days154 | Neuronal loss restricted to spinal cord |
| PDGF-β hα-syn (D-line)155 | PD (and DLB) | α-synuclein (wild-type) | Human PDGF-β | α- synuclein accumulation primarily in neocortex and limbic system, substantia nigra (rarely)156, motor deficits 9-12 months157 | α- synuclein aggregates not consistent with human Lewy bodies, no dopaminergic degeneration, glial expression of α- synuclein (protein and RNA) |
| mThy1 ha-syn158 | PD | α-synuclein (wild-type or A43T) | Mouse Thy1 | High α- synuclein expression in neocortex, limbic system, thalamus, some reports of spinal cord156 | No dopaminergic degeneration, few inclusions, mostly diffuse expression of α-synuclein |
| MPTP Neurotoxic lesion models159 | PD | Chemical lesion: MPTP | - | Dopaminergic degeneration | Acute models (not progressive models for onset), no α-synuclein inclusions in mice |
| YAC128160 | HD | htt (128 CAG repeats on exon 1) | Human HTT | Diffuse nuclear htt by 12mo, nuclear inclusions by 18mo, 15% reduction in striatal neuron count by 12mo | No cytoplasmic inclusions |
| HD94161 | HD | htt fragment (94 CAG repeats on exon 1)* | calmodulin-kinase IIα | Cytoplasmic and intranuclear inclusions in the striatum by 12 weeks old, striatal atrophy162 | No neuronal death |
*
Tetracycline-regulated transgene.