Research Models

PS19 with humanized TREM2 (common variant)

Synonyms: PS19-TREM2CV, PS19-T2CV

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Species: Mouse
Genes: MAPT, TREM2, Trem2
Mutations: MAPT P301S
Modification: MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out
Disease Relevance: Alzheimer's Disease, Frontotemporal Dementia
Strain Name: N/A
Genetic Background: C57BL/6
Availability: PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna.

Summary

These mice, referred to here as PS19-TREM2CV, carry transgenes encoding the common variant of human TREM2 and human MAPT with the P301S mutation linked to frontotemporal dementia, on a mouse-Trem2-null background. This model was generated by crossing PS19 mice on a Trem2-null background to animals carrying a TREM2 BAC, also on a Trem2-null background. The initial characterization of the line compared PS19-TREM2CV mice with PS19 mice carrying TREM2 with the R47H mutation (PS19-TREM2R47H) (Gratuze et al., 2020). These findings are described elsewhere.

PS19-TREM2CV mice have not yet been compared directly with PS19 mice expressing endogenous Trem2 or with wild-type mice. Nevertheless, cortical and hippocampal atrophy and ventricular enlargement were apparent in micrographs of brain sections from 9-month-old animals.

Modification Details

Trem2-/-PS19 mice (PS19 mice lacking endogenous mouse Trem2) were generated by back-crossing PS19 mice (The Jackson Laboratory, Catalog# 008169) to Trem2-/- mice (Turnbull et al., 2006). During the course of these crosses, animals were moved onto a C57BL/6 genetic background.

Trem2-/-PS19 mice were then crossed with transgenic mice that carry a BAC encoding the common variant of human TREM2, as well as TREML1 and TREML2, on a Trem2-null background.

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
  • Changes in LTP/LTD
  • Cognitive Impairment

Plaques

No data.

Tangles

Tangles revealed using antibody PG5 at 9 months.

Synaptic Loss

Fewer synapses and more dystrophic synapses, compared with PS19 mice carrying the R47H variant of TREM2.

Neuronal Loss

At 9 months, atrophy of hippocampus and entorhinal/piriform cortex and pronounced ventricular expansion. Thinning of the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex, compared with PS19 mice carrying TREM2-R47H.

Gliosis

Elevated expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the R47H variant of TREM2.

Changes in LTP/LTD

No data.

Cognitive Impairment

No data.

Last Updated: 14 Jul 2020

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References

Research Models Citations

  1. TREM2, humanized (common variant)
  2. PS19 with humanized TREM2 (R47H)
  3. Trem2 KO (Colonna) x PS19
  4. Tau P301S (Line PS19)
  5. Trem2 KO (Colonna)

Paper Citations

  1. Gratuze M, Leyns CE, Sauerbeck AD, St-Pierre MK, Xiong M, Kim N, Serrano JR, Tremblay MÈ, Kummer TT, Colonna M, Ulrich JD, Holtzman DM. Impact of TREM2R47H variant on tau pathology-induced gliosis and neurodegeneration. J Clin Invest. 2020 Sep 1;130(9):4954-4968. PubMed.
  2. Turnbull IR, Gilfillan S, Cella M, Aoshi T, Miller M, Piccio L, Hernandez M, Colonna M. Cutting edge: TREM-2 attenuates macrophage activation. J Immunol. 2006 Sep 15;177(6):3520-4. PubMed.

Other Citations

  1. Marco Colonna

External Citations

  1. The Jackson Laboratory, Catalog# 008169
  2. The Jackson Laboratory (Stock# 008169)

Further Reading