Research Models

Trem2 R47H KI x APOE4 (LOAD1)

Synonyms: APOE4/Trem2*R47H, APOE*4/Trem2*R47H, APOE4.Trem2*R47H

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Species: Mouse
Genes: APOE, Trem2
Modification: APOE: Knock-In; Trem2: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J

Summary

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

  • Plaques
  • Tangles
  • Neuronal Loss
  • Gliosis
  • Cognitive Impairment

No Data

  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

Not observed in cortex or hippocampus up to 24 months of age.

Tangles

Not observed in cortex or hippocampus up to 24 months of age.

Synaptic Loss

No data.

Neuronal Loss

Not observed in cortex or hippocampus up to 24 months of age.

Gliosis

Microgliosis not observed in cortex or hippocampus up to 24 months of age.

Changes in LTP/LTD

No data.

Cognitive Impairment

Age-related changes in locomotor activity, motor coordination, and working memory, but no genotype-dependent differences through 24 months of age, compared with wild-type mice.

Last Updated: 04 Oct 2023

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Trem2 KO (JAX)

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Species: Mouse
Genes: Trem2
Modification: Trem2: Knock-Out
Disease Relevance: Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease
Strain Name: C57BL/6J-Trem2em2Adiuj/J

Summary

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

No Data

  • Plaques
  • Tangles
  • Neuronal Loss
  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

Plaques

No data.

Tangles

No data.

Synaptic Loss

No data.

Neuronal Loss

No data.

Gliosis

No data.

Changes in LTP/LTD

No data.

Cognitive Impairment

No data.

Last Updated: 04 Oct 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Trem2 R47H KI (JAX)

Synonyms: MODEL-AD R47H, Trem2*R47HCSS (for cryptic splice site), B6.Trem2*R47H

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Species: Mouse
Genes: Trem2
Modification: Trem2: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: C57BL/6J-Trem2em1Adiuj/J

Summary

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

  • Plaques
  • Tangles
  • Neuronal Loss
  • Cognitive Impairment

No Data

  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

Not observed in cortex or hippocampus up to 24 months of age.

Tangles

Not observed in cortex or hippocampus up to 24 months of age.

Synaptic Loss

No data.

Neuronal Loss

Not observed in cortex or hippocampus up to 24 months of age.

Gliosis

No data.

Changes in LTP/LTD

No data.

Cognitive Impairment

Locomotor activity, motor coordination, and working memory similar to wild-type at 2 and 12 months of age.

Last Updated: 04 Oct 2023

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Trem2 T66M KI

Synonyms: Trem2 p.T66M

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Species: Mouse
Genes: Trem2
Modification: Trem2: Knock-In
Disease Relevance: Frontotemporal Dementia
Strain Name: Trem2em1Bwef

Summary

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

  • Plaques
  • Tangles

No Data

  • Neuronal Loss
  • Synaptic Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

Last Updated: 08 Mar 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

FUSDelta14 Knock-in

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Species: Mouse
Genes: FUS
Mutations: FUSDelta14 truncation mutation
Modification: FUS: Knock-In
Disease Relevance: Amyotrophic Lateral Sclerosis
Strain Name: B6N;B6J-Fustm1Emcf/H

Summary

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

  • Cytoplasmic Inclusions

No Data

  • Cortical Neuron Loss
  • Muscle Atrophy
  • Body Weight
  • Gliosis

Cortical Neuron Loss

No data.

Lower Motor Neuron Loss

No lower motor neuron loss at 3 months but 14% reduction in the number of motor neurons in lumbar spinal cord at 12 months and 20% reduction by 18 months.

Cytoplasmic Inclusions

No increase in the number of spinal motor neurons that contain p62- or ubiquitin-positive inclusions in aged FUSDelta14 mice compared with aged wild-type mice.

Gliosis

No data.

NMJ Abnormalities

Reduction in the number of intact neuromuscular junctions (fully innervated endplates) in hindlimb lumbrical muscles by 18 months of age.

Muscle Atrophy

No data.

Motor Impairment

Normal motor activity at 3 months of age but impaired hindlimb function by 15 months.

Body Weight

No data.

Premature Death

Reduced survival starting at 19 months of age.

Last Updated: 01 Dec 2017

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

E2FAD

Synonyms: APOE2-FAD, APOE2 Targeted Replacement x 5xFAD

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Species: Mouse
Genes: APOE, APP, PSEN1
Modification: APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A

The E4FAD, E3FAD, and E2FAD mouse models are crosses between the widely used 5xFAD mice (Tg6799 line) and the APOE4, APOE3, and APOE2 Targeted Replacement mice, respectively. These models were created to study the role of the three human isoforms of APOE on AD phenotypes. The mice described here were homozygous for the APOE allele and heterozygous of the 5xFAD mutations. In general, the EFAD mice display less severe phenotypes relative to the 5xFAD line.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

No Data

  • Tangles
  • Neuronal Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

Plaques

Plaques develop in the subiculum and deep cortical layers by 4 months.

Tangles

No data.

Synaptic Loss

Protein levels of  NMDA receptor subunits decreased from 2 to 6 months.

Neuronal Loss

No data.

Gliosis

Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

Changes in LTP/LTD

No data.

Cognitive Impairment

E2FAD mice had performance in learning and memory tasks comparable to E3FAD animals and better than E4FAD mice.

Last Updated: 09 Jun 2017

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

E3FAD

Synonyms: APOE3-FAD, APOE3 Targeted Replacement x 5xFAD

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Species: Mouse
Genes: APOE, APP, PSEN1
Modification: APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A

The E4FAD, E3FAD, and E2FAD mouse models are crosses between the widely used 5xFAD mice (Tg6799 line) and the APOE4, APOE3, and APOE2 Targeted Replacement mice, respectively. These models were created to study the role of the three human isoforms of APOE on AD phenotypes. The mice described here were homozygous for the APOE allele and heterozygous of the 5xFAD mutations. In general, the EFAD mice display less severe phenotypes relative to the 5xFAD line.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

No Data

  • Tangles
  • Neuronal Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

Plaques

Plaques develop in the subiculum and deep cortical layers by 4 months.

Tangles

No data.

Synaptic Loss

Protein levels of  NMDA receptor subunits decreased from 2 to 6 months.

Neuronal Loss

No data.

Gliosis

Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

Changes in LTP/LTD

No data.

Cognitive Impairment

E3FAD mice had performance in learning and memory tasks comparable to E4FAD and E2FAD animals.

Last Updated: 09 Jun 2017

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

E4FAD

Synonyms: APOE4-FAD, APOE4 Targeted Replacement x 5xFAD

Tools

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Species: Mouse
Genes: APOE, APP, PSEN1
Modification: APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A

The E4FAD, E3FAD, and E2FAD mouse models are crosses between the widely used 5xFAD mice (Tg6799 line) and the APOE4, APOE3, and APOE2 Targeted Replacement mice, respectively. These models were created to study the role of the three human isoforms of APOE on AD phenotypes. The mice described here were homozygous for the APOE allele and heterozygous of the 5xFAD mutations. In general, the EFAD mice display less severe phenotypes relative to the 5xFAD line.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

No Data

  • Tangles
  • Neuronal Loss
  • Changes in LTP/LTD

Plaques

Plaques develop in the subiculum and deep cortical layers by 4 months.

Tangles

No data.

Synaptic Loss

Decreased protein levels of PSD95 and NMDA receptor subunits by 4 months.

Neuronal Loss

No data.

Gliosis

Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

Changes in LTP/LTD

No data.

Cognitive Impairment

Modest learning deficits in the Morris water maze by 2 months. Progressive decrease in performance on learning and memory tasks. 

Last Updated: 09 Jun 2017

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

FusΔNLS

Synonyms: Fus-dNLS, Fus-deltaNLS, Fus-ΔNLS/+

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Species: Mouse
Genes: Fus
Mutations: FUS ΔNLS
Modification: Fus: Knock-In
Disease Relevance: Amyotrophic Lateral Sclerosis
Strain Name: N/A

Summary

FUS (Fused in Sarcoma) is a member of a family of RNA-binding proteins with roles in transcription, RNA processing, RNA transport, and translation. Mutations in FUS, many of which are clustered near the nuclear localization signal (NLS) at the C-terminus, are linked to familial cases of ALS. Additionally, truncation and frameshift mutations can result in the deletion of the NLS.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Absent

  • Body Weight
  • Premature Death

No Data

  • Cortical Neuron Loss
  • Muscle Atrophy

Cortical Neuron Loss

No data.

Lower Motor Neuron Loss

Approximately 30% reduction of motor neuron numbers in the dorsal spinal cord.

Cytoplasmic Inclusions

Ubiquitin pathology was observed in motor neurons, but p62 inclusions were not.

Gliosis

Slight increase in oligodendrocytes in the spinal cord white matter.

NMJ Abnormalities

Fibrillation and fasciculation potentials were observed in the gastrocnemius or tibialis anterior muscles. There was also a reduction in compound muscle action potential amplitude.

Muscle Atrophy

No data.

Motor Impairment

By 10 months, mice demonstrated irregular walking patterns and reduced hang time on the inverted grid test. No deficits in grip strength or rotarod performance. Paralysis was not observed.

Body Weight

By 22 months, no weight loss was observed.

Premature Death

Life span was not altered.

Last Updated: 12 May 2017

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

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