Research Models
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5 Models
5 Visualizations
AD-related Research Models
Phenotypes Examined
- Plaques
- Tangles
- Neuronal Loss
- Gliosis
- Synaptic Loss
- Changes in LTP/LTD
- Cognitive Impairment
When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.
C9-BAC500 (Brown)
Observed
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Cytoplasmic Inclusions at 40
No cytoplasmic mislocalization, or aggregation of TDP-43 in the motor cortex. However, dipeptide repeats accumulated at advanced age and formed small perinuclear inclusion bodies positive for poly-GP.
Absent
-
Motor Impairment at
No overt motor deficit as measured by the Rotarod and grip strength.
-
Cortical Neuron Loss at
Not observed.
-
Lower Motor Neuron Loss at
Not observed.
-
NMJ Abnormalities at
No difference in denervation of neuromuscular junctions at 24 months of age. No difference in motor or sensory spinal nerve root axon number or morphology.
-
Body Weight at
Non-significant trend for male C9BAC mice to be heavier than non-Tg controls. Female data have not yet been reported.
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Premature Death at
Normal lifespan beyond 2 years in male mice. Female data have not yet been reported.
-
Gliosis at
No signs of increased activation of microglia or astrocytes in the brain or spinal cord.
No Data
-
Muscle Atrophy at
Muscle histology has not been reported, but no overt muscle atrophy was observed.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| C9orf72 | Hexanucleotide repeat in C9ORF72 | C9orf72: Transgenic | Amyotrophic Lateral Sclerosis, Frontotemporal Dementia | Widespread RNA foci throughout the nervous system starting at 3 months of age, especially comprised of sense transcript. Dipeptide repeats (e.g., poly-GP) as soluble protein and insoluble aggregates. No neurodegeneration. No TDP-43 aggregation, gliosis, inflammation, or synapse loss. |
No overt behavioral abnormalities compared to non-Tg controls. Assessment included grip strength, Rotarod performance, and intruder test. |
C9-BACexp (Baloh/Lutz)
Observed
-
Cytoplasmic Inclusions at 13
RNA foci throughout the nervous system starting at 3 months of age. Foci comprised of RNA transcripts in both the sense and antisense directions. Age-associated formation of dipeptide aggregates, e.g., poly-GP.
Absent
-
Motor Impairment at
No abnormalities in grip strength, Rotarod performance, or open-field testing at a young age (3 months) or advanced age (18 months), compared with non-Tg controls.
-
Cortical Neuron Loss at
Not observed.
-
Lower Motor Neuron Loss at
Not observed.
-
NMJ Abnormalities at
Not observed.
-
Muscle Atrophy at
Not observed.
-
Body Weight at
No abnormalities in body weight at a young age (3 months) or advanced age (18 months) compared with non-Tg controls.
-
Premature Death at
Normal lifespan.
-
Gliosis at
No increase in GFAP staining in the brain and spinal cord compared with non-Tg controls, even at 18 months of age.
No Data
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| C9orf72 | Hexanucleotide repeat in C9ORF72 | C9orf72: Transgenic | Amyotrophic Lateral Sclerosis, Frontotemporal Dementia | Widespread RNA foci throughout the nervous system first assessed at 3 months of age. Soluble dipeptide repeats (e.g., poly-GP) and insoluble aggregates. No neurodegeneration. No TDP-43 aggregation, gliosis, inflammation, or obvious synapse loss. |
No behavioral abnormalities compared to non-Tg controls at either young age (3 months) or advanced age (18 months). Tests included: grip strength, Rotarod performance, open-field, three-chamber, and Y-maze. |
C9ORF72(AAV)(G4C2)149
Observed
-
Motor Impairment at 24
Deficits in the hanging wire test emerge between 3 and 6 months.
-
Cortical Neuron Loss at 24
Cortical neuron loss by 6 months.
-
Cytoplasmic Inclusions at 12
Cytoplasmic inclusions containing dipeptide repeat proteins (DPRs) derived from sense RNA seen in the cortex, hippocampus, cerebellum, and spinal cord; inclusions containing DPRs produced from antisense transcripts seen in the cortex and occasionally in the hippocampus.
-
Gliosis at 12
Astrogliosis in the cortex by 3 months.
Absent
No Data
-
Lower Motor Neuron Loss at
No data.
-
NMJ Abnormalities at
No data.
-
Muscle Atrophy at
No data.
-
Body Weight at
No data.
-
Premature Death at
No data.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| C9orf72 | Hexanucleotide repeat in C9ORF72 | C9orf72: Virus | Amyotrophic Lateral Sclerosis, Frontotemporal Dementia | Intranuclear foci containing antisense and antisense repeat RNA; cytoplasmic inclusions containing sense and antisense dipeptide repeat proteins; accumulation of phosphorylated TDP-43 and stress granule-associated proteins; neuron loss and gliosis. |
Motor and cognitive deficits emerge between 3 and 6 months of age. Hyperactivity seen by 3 months. |
C9ORF72(AAV)(G4C2)66
Observed
-
Motor Impairment at 26
At 6 months, 66-repeat mice perform as well as 2-repeat mice on the Rotarod on the first day of testing. However, they fail to improve during subsequent trials, suggesting impairments in coordination and/or motor learning.
-
Cortical Neuron Loss at 26
Compared with mice expressing 2-repeats, the 66-repeat mice had 17 percent fewer neurons in the cortex at 6 months of age and 11 percent fewer Purkinje cells in the cerebellum. At this age neurons in the hippocampus and thalamus were not affected.
-
Cytoplasmic Inclusions at 26
By 6 months, inclusions of C9RAN dipeptides were present in neurons of the cortex and hippocampus, and to a lesser extent in the cerebellum and spinal cord. Inclusions contained polyGA, polyGP, and polyGR dipeptides and were largely ubiquitin-positive.
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Body Weight at 26
At 6 months females had a lower body weight than mice expressing 2-repeats. Body weight did not differ in males.
-
Gliosis at 26
Astrogliosis in the cortex by 6 months.
Absent
-
Lower Motor Neuron Loss at
At 6 months, neuronal loss in the spinal cord was not detected.
No Data
-
NMJ Abnormalities at
No data.
-
Muscle Atrophy at
No data.
-
Premature Death at
No data.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| C9orf72 | Hexanucleotide repeat in C9ORF72 | C9orf72: Virus | Amyotrophic Lateral Sclerosis, Frontotemporal Dementia | Nuclear RNA foci in neurons, dipeptide aggregates (GA, GP, and GR), cytoplasmic inclusions of phosphorylated TDP-43, neuronal loss, brain atrophy, and gliosis. |
Subtle behavioral deficits including anxiety-like behavior, hyperactivity, and antisocial behavior. Subtle motor impairment and failure to improve on the Rotarod. |
C9orf72 Knock-out
Observed
-
Motor Impairment at 39
Reduced activity on open-field test. No abnormalities in grip strength or Rotarod performance.
Absent
-
Cortical Neuron Loss at
Not observed.
-
Lower Motor Neuron Loss at
Not observed.
-
Cytoplasmic Inclusions at
Not observed.
-
NMJ Abnormalities at
Not observed.
-
Muscle Atrophy at
Not observed.
-
Body Weight at
Not observed.
-
Premature Death at
Not observed.
-
Gliosis at
Not observed.
No Data
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| C9orf72 | C9orf72: Knock-Out | Frontotemporal Dementia, Amyotrophic Lateral Sclerosis | Chromatolytic structures are observed with H&E staining, in gray and white matter of the spinal cord. Neurodegeneration not present. |
Normal sensorimotor coordination and limb strength. Reduced activity in open-field test. |
ALS-related Research Models
- Sex-specific differences
- Cortical Neuron Loss
- Lower Motor Neuron Loss
- Cytoplasmic Inclusions
- Gliosis
- NMJ Abnormalities
- Muscle Atrophy
- Motor Impairment
- Body Weight
- Premature Death