Table 2.
Summary of Commonly Used FTD Mouse Models
| Models | Description | AD-like pathology | Neuron loss | Cognitive impairment and behavioral changes | References |
|---|---|---|---|---|---|
| Tau/MAPT models | |||||
| Tg4510 | Transgenic model with tetracycline-inducible expression of human Tau with P301L mutation | Tauopathy at 2.5 months | ∼60% CA1 neuron loss at 5.5 months | Impaired spatial learning and memory at 2.5 months; LTP impairment at 4.5 months; motor impairment starting at 6 months; ∼30% dendritic spine loss at 8 months; forebrain atrophy at 10 months | Ramsden et al, 200584 |
| Tau (P301L) | Transgenic model carrying human Tau with P301L mutation | Tauopathy at 8 months | N.A. | Spine density is higher in young mice; cognitive impairment begins at 5 months; LTP deficit at 6 months | Lee et al, 202148; Buchholz and Zempel, 202485 |
| PS19-P301S | Transgenic model carrying human Tau with P301S mutation | Tauopathy at 6 months | Hippocampal neuron loss at 9 months | Synaptic loss at 3 mo, LTP decline at 6 months; impairment in spatial learning and memory at 6 months; motor deficit progression to paralysis at 7–10 months | Schindowski et al, 200686 |
| Progranulin/GRN models | |||||
| Grn KO | Progranulin/GRN knock-out model | TDP-43 pathology in knock-out mice at 12–18 months | Absent | Social behavior deficits at 1–2 months, depression and disinhibition behavior at 3–4 months, cognitive impairment at 12 months | Filiano et al, 201387 |
| GrnR493X KI | Knock-in mice carrying R493X mutation | TDP-43 pathology in homozygotes mice at 12 months | Neuron loss in motor cortex in end-stage mice | Cognitive impairment in learning, memory, social, and emotion in homozygote mice at 11 months | Nguyen et al, 201888 |
| C9orf72 models | |||||
| BAC (G4C2)450 | BAC transgenic carrying a partial human C9orf72 gene with a (G4C2)450 repeat region | pTDP-43 increase in 22 months | No motor neuron loss | Increased anxiety and cognitive impairment starting at 4–6 months, worse at 12–18 months | Jiang et al, 201689 |
| BAC (G4C2)500 | BAC transgenic carrying full human C9orf72 gene with a (G4C2)500 repeat region | TDP-43 inclusions in symptomatic mice at 18 months | Cortical layer V neuron loss at 8 months | Motor impairment at 4 months, paralysis and mortality between 5 and 8 months, survived mice showed anxiety-like behavior at 1 year | Jiang et al, 201689; Liu et al, 201690 |
AD, Alzheimer disease; BAC, bacterial artificial chromosome approach; LTP, long-term potentiation; N.A., not applicable; TDP, transactive response DNA-binding protein.