Research Models

Find A Model By Name

Search Research Models

Search Results

5 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathology Behavior/Cognition Other Phenotype Availability Primary Paper Visualization
Mouse Models (5)
<p>Brown</p>, <p>C9-BAC[GGGGCC]500</p> SJL/B6 C9orf72 Hexanucleotide repeat in C9ORF72 This transgenic mouse carries a bacterial artificial chromosome (BAC) containing exons 1 through 6 of human C9orf72 with ~500 GGGGCC repeat motifs and ~140.5 kb upstream. 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. Viable, fertile, born in Mendelian ratios. Available through Robert Brown Peters et al., 2015 Yes
Baloh/Lutz, C9-BAC[GGGGCC]100-1000, Tg(C9orf72_3) line 112, Line F112 C57BL/6J-Tg(C9orf72_i3)112Lutzy/J C57BL/6J C9orf72 Hexanucleotide repeat in C9ORF72 This transgenic mouse carries a bacterial artificial chromosome (BAC) containing full-length human C9ORF72 sequence with ~100-1000 repeats. 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. Viable, fertile, born in Mendelian ratios. The Jackson Lab: Stock# 023099; Live O'Rourke et al., 2015 Yes
<p>-</p>, <p>(G<sub>4</sub>C<sub>2</sub>)<sub>149</sub></p>, <p>149-repeat mice</p> C57BL/6J C9orf72 Hexanucleotide repeat in C9ORF72 An adeno-associated viral (AAV) vector was used to deliver 149 repeats of the hexanucleotide GGGGCC motif, along with the 5' (119 bp) and 3' (100 bp) flanking regions of the C9ORF72 gene, driven by the β-actin promoter. Virus was injected into the lateral ventricles of wild-type pups on postnatal day 0. 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. Mislocalization of RanGAP1 suggests nucleocytoplasmic transport defects. Unknown. Chew et al., 2019 Yes
<p>-</p>, <p>66-repeat mice</p>, <p>Petrucelli’s AAV C9 model</p> C57BL/6 C9orf72 Hexanucleotide repeat in C9ORF72 An adeno-associated viral (AAV) vector was used to deliver a sequence of 66 repeats of the hexanucleotide, GGGGCC. The virus was injected into the cerebral ventricles of P0 pups. 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. Reduced body weight in females by 6 months. Viral construct available through Leonard Petrucelli Chew et al., 2015 Yes
<p>-</p>, <p>C9orf72 KO</p>, <p>3110043O21Rik Knock-out</p> 3110043O21Riktm1(KOMP)Mbp C57BL/6N C9orf72 The mouse 3110043O21Rik gene (homologue of human C9orf72) was inactivated by deleting a region containing exons 2-6, which includes the start codon. The targeting vector contained expression cassettes, flanked by FRT sites, for lacZ and neo as selectable markers. 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. Spleens and lymph nodes enlarged by 1 month, size increases with age. Histology shows enlarged debris-filled cells. Available through the UC Davis Knockout Mouse Project (KOMP) Repository, gene 3110043021Rik; Cryopreserved O'Rourke et al., 2016 Yes

5 Visualizations

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

C9-BAC500 (Brown)

  • Absent
  • Absent
  • Observed
  • Absent
  • Absent
  • No Data
  • Absent
  • Absent
  • Absent

Not observed.

Not observed.

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.

No signs of increased activation of microglia or astrocytes in the brain or spinal cord.

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.

Muscle histology has not been reported, but no overt muscle atrophy was observed.

No overt motor deficit as measured by the Rotarod and grip strength.

Non-significant trend for male C9BAC mice to be heavier than non-Tg controls. Female data have not yet been reported.

Normal lifespan beyond 2 years in male mice. Female data have not yet been reported.

C9-BACexp (Baloh/Lutz)

  • Absent
  • Absent
  • Observed
  • Absent
  • Absent
  • Absent
  • Absent
  • Absent
  • Absent

Not observed.

Not observed.

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.

No increase in GFAP staining in the brain and spinal cord compared with non-Tg controls, even at 18 months of age.

Not observed.

Not observed.

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.

No abnormalities in body weight at a young age (3 months) or advanced age (18 months) compared with non-Tg controls.

Normal lifespan.

C9orf72 Knock-out

  • Absent
  • Absent
  • Absent
  • Absent
  • Absent
  • Absent
  • Observed
  • Absent
  • Absent

Not observed.

Not observed.

Not observed.

Not observed.

Not observed.

Not observed.

Reduced activity on open-field test. No abnormalities in grip strength or Rotarod performance.

Not observed.

Not observed.

C9ORF72(AAV)(G4C2)149

  • Observed
  • No Data
  • Observed
  • Observed
  • No Data
  • No Data
  • Observed
  • No Data
  • No Data

Cortical neuron loss by 6 months.

No data.

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.

Astrogliosis in the cortex by 3 months.

No data.

No data.

Deficits in the hanging wire test emerge between 3 and 6 months.

No data.

No data.

C9ORF72(AAV)(G4C2)66

  • Observed
  • Absent
  • Observed
  • Observed
  • No Data
  • No Data
  • Observed
  • Observed
  • No Data

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.

At 6 months, neuronal loss in the spinal cord was not detected.

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.

Astrogliosis in the cortex by 6 months.

No data.

No data.

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.

At 6 months females had a lower body weight than mice expressing 2-repeats. Body weight did not differ in males.

No data.

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

C9-BAC500 (Brown)

Absent

Not observed.

Absent

Not observed.

Observed

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

No signs of increased activation of microglia or astrocytes in the brain or spinal cord.

Absent

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.

No Data

Muscle histology has not been reported, but no overt muscle atrophy was observed.

Absent

No overt motor deficit as measured by the Rotarod and grip strength.

Absent

Non-significant trend for male C9BAC mice to be heavier than non-Tg controls. Female data have not yet been reported.

Absent

Normal lifespan beyond 2 years in male mice. Female data have not yet been reported.

C9-BACexp (Baloh/Lutz)

Absent

Not observed.

Absent

Not observed.

Observed

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

No increase in GFAP staining in the brain and spinal cord compared with non-Tg controls, even at 18 months of age.

Absent

Not observed.

Absent

Not observed.

Absent

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.

Absent

No abnormalities in body weight at a young age (3 months) or advanced age (18 months) compared with non-Tg controls.

Absent

Normal lifespan.

C9orf72 Knock-out

Absent

Not observed.

Absent

Not observed.

Absent

Not observed.

Absent

Not observed.

Absent

Not observed.

Absent

Not observed.

Observed

Reduced activity on open-field test. No abnormalities in grip strength or Rotarod performance.

Absent

Not observed.

Absent

Not observed.

C9ORF72(AAV)(G4C2)149

Observed

Cortical neuron loss by 6 months.

No Data

No data.

Observed

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.

Observed

Astrogliosis in the cortex by 3 months.

No Data

No data.

No Data

No data.

Observed

Deficits in the hanging wire test emerge between 3 and 6 months.

No Data

No data.

No Data

No data.

C9ORF72(AAV)(G4C2)66

Observed

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.

Absent

At 6 months, neuronal loss in the spinal cord was not detected.

Observed

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.

Observed

Astrogliosis in the cortex by 6 months.

No Data

No data.

No Data

No data.

Observed

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.

Observed

At 6 months females had a lower body weight than mice expressing 2-repeats. Body weight did not differ in males.

No Data

No data.