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.
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.
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.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Changes in LTP/LTD
- Cognitive Impairment
Tangles revealed using antibody PG5 at 9 months.
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.
Elevated expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the R47H variant of TREM2.
Fewer synapses and more dystrophic synapses, compared with PS19 mice carrying the R47H variant of TREM2.
Changes in LTP/LTD
Last Updated: 14 Jul 2020
Research Models Citations
- TREM2, humanized (common variant)
- PS19 with humanized TREM2 (R47H)
- Trem2 KO (Colonna) x PS19
- Tau P301S (Line PS19)
- Trem2 KO (Colonna)
- 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.
- 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.