Research Models

APP+PS1

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Species: Rat
Genes: APP, PSEN1
Modification: APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A

Summary

APP+PS1 transgenic rats express human APP with the Swedish and Indiana mutations and human PSEN1 with the L166P mutation. Both transgenes are driven by the ubiquitin-C promoter. These rats exhibit amyloid pathology, neurodegeneration, and behavioral deficits.

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
  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

Abundant plaques in hippocampus and subiculum, scattered plaques in cortex.

Tangles

No data.

Synaptic Loss

No data.

Neuronal Loss

Necrotic neurons in hippocampus and cortex.

Gliosis

No data.

Changes in LTP/LTD

No data.

Cognitive Impairment

Deficits in Barnes maze at 10 months.

Last Updated: 31 Aug 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

APP21

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Species: Rat
Genes: APP
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: F344-Tg(APP)21Besey

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

No Data

  • Tangles
  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

Do not spontaneously develop amyloid pathology, but can serve as hosts for exogenously seeded amyloid deposits.

Tangles

“Flame-shaped” profiles in hippocampal neurons of 18- to 19-month-old female rats revealed by hematoxylin-and-eosin-staining.

Synaptic Loss

No data.

Neuronal Loss

Necrotic neurons in hippocampus and cortex of female rats.

Gliosis

Activated (MHCII-positive) microglia present in white matter tracts at 15 months.

Changes in LTP/LTD

No data.

Cognitive Impairment

Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.

Last Updated: 31 Aug 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Tardbp Q331K Knock-In

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Species: Mouse
Genes: Tardbp
Mutations: Tardp Q331K
Modification: Tardbp: Knock-In
Disease Relevance: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Strain Name: N/A

Summary

CRISPR/Cas9 was used to introduce the p.Q331K mutation into the mouse Tardp gene (Fratta et al., 2018). These mice can be used to study the effects of the p.Q331K mutation when TDP-43 is expressed at physiological levels, under the control of its natural regulatory elements.

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

  • Motor Impairment
  • Cortical Neuron Loss
  • Lower Motor Neuron Loss
  • Cytoplasmic Inclusions
  • NMJ Abnormalities
  • Muscle Atrophy
  • Body Weight
  • Premature Death
  • Gliosis

Cortical Neuron Loss

No data.

Lower Motor Neuron Loss

No data.

Cytoplasmic Inclusions

No data.

Gliosis

No data.

NMJ Abnormalities

No data.

Muscle Atrophy

No data.

Motor Impairment

No data.

Body Weight

No data.

Premature Death

No data.

Last Updated: 17 Aug 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Tardp_RRM2mut

Synonyms: RRM2mut

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Species: Mouse
Genes: Tardbp
Mutations: Tardp F210I
Modification: Tardbp: Other
Disease Relevance: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Strain Name: Tardbp F210I

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

  • Motor Impairment
  • Lower Motor Neuron Loss
  • Cytoplasmic Inclusions
  • NMJ Abnormalities
  • Premature Death

No Data

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

Cortical Neuron Loss

No data.

Lower Motor Neuron Loss

Not observed at 2 years.

Cytoplasmic Inclusions

Not observed at 2 years.

Gliosis

No data.

NMJ Abnormalities

Not observed at 2 years.

Muscle Atrophy

No data.

Motor Impairment

Not observed at 2 years.

Body Weight

No data.

Premature Death

Homozygous mutation is embryonic lethal.

Last Updated: 17 Aug 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Tardp LCDmut

Synonyms: LCDmut

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Species: Mouse
Genes: Tardbp
Mutations: Tardbp M323K
Modification: Tardbp: Other
Disease Relevance: Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Strain Name: Tardbp M323K

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

  • Premature Death

No Data

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

Cortical Neuron Loss

No data.

Lower Motor Neuron Loss

28 percent reduction in the number of motor neurons in the sciatic motor neuron pool, compared with non-transgenic littermates.

Cytoplasmic Inclusions

At 18 months of age, p62- and ubiquitin-positive inclusions are found in the ventral regions of the spinal cord, although these inclusions do not appear to be located in the cytoplasm of motor neurons.

Gliosis

No data.

NMJ Abnormalities

By 24 months, a 15 percent reduction in motor units innervating the extensor digitorum muscle.

Muscle Atrophy

No data.

Motor Impairment

Grip strength in both male and female mice begins to decline at 12 months of age. By 24 months, there is a nearly 40 percent reduction in force measured in tibialis anterior muscles.

Body Weight

No data.

Premature Death

Do not exhibit premature death, at least until 24 months of age.

Last Updated: 17 Aug 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Trem2 R47H KI (Lamb/Landreth) X APPPS1-21

Synonyms: APPPS1-21;Trem2+/R47H

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Species: Mouse
Genes: Trem2, APP, PSEN1
Modification: Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A

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

  • Tangles
  • Neuronal Loss

No Data

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

Plaques

Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, compared with APPPS1-21 mice homozygous for wild-type Trem2.

Tangles

Tangles were not observed at 4 months of age, but hyperphosphorylated tau was detected in dystrophic neurites surrounding plaques.

Synaptic Loss

No data.

Neuronal Loss

No differences in neuron number in cotical layer V in APPPS1-21;Trem2+/R47H mice relative to APPPS1-21 mice homozygous for wild-type Trem2, at 4 months of age.

Gliosis

Fewer plaque-associated myeloid cells in APPPS1-21;Trem2+/R47H, compared with APPPS1-21 mice homozygous for wild-type Trem2.

Changes in LTP/LTD

No data.

Cognitive Impairment

No data.

Last Updated: 03 Aug 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Trem2 R47H KI (Lamb/Landreth)

Synonyms: Trem2+/R47H

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Species: Mouse
Genes: Trem2
Modification: Trem2: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: N/A

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

No Data

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

Plaques

No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age.

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: 05 Aug 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

App KO/APOE4/Trem2*R47H

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Species: Mouse
Genes: APOE, App, Trem2
Modification: APOE: Knock-In; App: Knock-Out; Trem2: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: B6.Cg-Apoetm1.1(APOE*4)Adiuj Appem2Adiuj Trem2em1Adiuj/J

Summary

The epsilon-4 allele of Apoliporotein E (APOE4) and the R47H variant of TREM2 have each been found to confer an approximately threefold increased risk for Alzheimer’s disease in humans heterozygous for either allele.  This triple mutant line carries a humanized APOE4 gene, the p.R47H mutation knocked into mouse Trem2, and a 94-bp deletion in exon 14 (APP695 numbering) of the mouse App gene. This line may be useful for studying late-onset, sporadic Alzheimer's disease.

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: 30 Nov 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

hAbeta-loxP-KI

Synonyms: hAbeta-loxP-KI on mixed B6J and B6NJ

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Species: Mouse
Genes: APP
Modification: APP: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: B6(SJL)-Apptm1.1Aduci/J

Summary

These mice express APP with a “humanized” Aβ sequence. Three point mutations were introduced into exon 14 (exon numbering according to APP695, with 16 exons) of the mouse App gene, to produce three amino acid substitutions within the Aβ sequence (amino acids 5 (G to R), 10 (F to Y) and 13 (R to H) of Aβ). Exon 14 is also flanked by loxP sites. The human Aβ generated by these mice is expected to be more aggregation-prone than the endogenous mouse Aβ. This line may be useful for studying late-onset sporadic Alzheimer’s disease.

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: 09 Apr 2019

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

Research Models

Plcg2*M28L/APOE4/Trem2*R47H

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Species: Mouse
Genes: APOE, Plcg2, Trem2
Modification: APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In
Disease Relevance: Alzheimer's Disease
Strain Name: B6.Cg-Apoetm1.1(APOE*4)Adiuj Plcg2em2Adiuj 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

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: 30 Nov 2018

COMMENTS / QUESTIONS

No Available Comments

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Further Reading

No Available Further Reading

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