Research Models

TauC3 (Transgenic caspase-cleaved tau)

Species: Mouse
Genes: MAPT
Modification: MAPT: Transgenic
Disease Relevance: Alzheimer's Disease, Frontotemporal Dementia
Strain Name: N/A
Genetic Background: BALB/C
Availability: Unknown

Summary

These mice express a truncated form of human tau protein called TauC3, which lacks 20 amino acids at the C-terminus and thus mimics the tau fragment produced by caspase cleavage. Memory deficits occur very early in this model, although the mice never develop significant neurodegeneration or neuroinflammation. Transgene expression is restricted to the brain and occurs at levels lower than endogenous tau expression. Although TauC3 mice do not develop overt tangle pathology, they accumulate hyperphosphorylated tau from a young age, including hyperphosphorylated tau oligomers and insoluble aggregates (Kim et al., 2015).

TauC3 mice, both male and female, develop early deficits in learning and memory as assessed by several behavioral tests. Impaired spatial memory, as measured by the Y-maze, was apparent as early as 1.3 months of age and worsened with time. TauC3 mice also showed deficits in the novel object recognition test and in passive-avoidance tests. Their overall activity level was in the normal range and they had no deficits in the wire-hang test, suggesting normal motor function.

Memory deficits do not appear to be attributable to neuronal loss, which was minimal in this model, even at advanced ages. Although, a few TUNEL-positive cells appeared in the hippocampi and cortices of six-month old mice, there was no significant cell death by 12 months of age. Likewise, astrogliosis was comparable to levels in non-Tg mice. Synaptic loss was suggested by decreased levels of synaptic proteins such as synaptophysin, PSD95, and subunits of the NMDA receptor. Expression of transgenic protein was confirmed within the cortex, hippocampus, striatum, and cerebellum.

Neurofibrillary tangles were not detected at any age, however, insoluble filamentous aggregates were observed in the hippocampus and cortex by three months of age and increased by six months of age. Abnormally hyperphosphorylated tau occurred early; by 1.3 months TauC3 mice had elevated levels of phospho-tau at a variety of epitopes, including serine 202, threonine 231, serine 262/356, and serine 396/404. In addition, staining with the MC-1 antibody (Jicha et al., 1997) indicated early conformational changes suggestive of pre-tangle pathology.

The lifespan of hemizygous male and female TauC3 mice was normal.

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

No Data

  • Changes in LTP/LTD

Plaques

Amyloid plaques were absent.

Tangles

Neurofibrillary tangles were not observed; however, hyperphosphorylated tau occurred early in the form of oligomers and aggregates.

Neuronal Loss

No significant neurodegeneration by 12 months of age.

Gliosis

No significant astrogliosis in the hippocampus or cortex by 12 months of age.

Synaptic Loss

Reduced levels of synaptic proteins as early as 1.3 months, including synaptophysin. Further reductions in 3 and 6-month-old animals.

Changes in LTP/LTD

Unknown.

Cognitive Impairment

Learning and memory impairments as early as 1.3 months in several behavioral tests including the Y-maze, passive avoidance, and novel object recognition.

Last Updated: 08 Jan 2016

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References

Paper Citations

  1. . Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model. Neurobiol Dis. 2016 Mar;87:19-28. Epub 2015 Dec 17 PubMed.
  2. . Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau. J Neurosci Res. 1997 Apr 15;48(2):128-32. PubMed.

Further Reading

No Available Further Reading