Research Models

THY-Tau22

Synonyms: Tau22

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Species: Mouse
Genes: MAPT
Mutations: MAPT G272V, MAPT P301S
Modification: MAPT: Transgenic
Disease Relevance: Frontotemporal Dementia, Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL6/CBA; backcrossed to C57BL6
Availability: Available through Luc Buée

Summary

THY-Tau22 mice are a model for tau aggregation, a pathological hallmark of Alzheimer's disease as well as numerous tauopathies. With age these mice develop a variety of tau-related neuropathological changes, including tau hyperphosphorylation, neurofibrillary-like tau inclusions, and ghost tangles. Tau pathology is generally mild at three to four months of age, moderate at six to seven months, and extensive at nine months and beyond.  

In these mice levels of human tau increase with age. At three months heterozygous mice have four to five-fold higher levels of human tau than endogenous tau in the cortex. At twelve months, levels are approximately five to six-fold higher. Levels are slightly lower in the hippocampus. Only trace levels are detected in the spinal cord (Schindowski et al., 2006).

Behaviorally, these mice display learning and memory diffculties, including deficits in spatial, social, and contextual learning that cannot be attributed to a neuromotor impairment. The mice do not exhibit changes in overall motor activity and do not have gross motor deficits (Schindowski et al., 2006). Non-spatial memory was affected as early as six months, whereas spatial is impaired later, after nine months (Van der Jeugd et al., 2013). Impaired appetitive responding has also been observed (Lo et al., 2013).

The neuropathology and behavioral changes coincide with changes in hippocampal synaptic plasticity. Although LTP appears to be intact, deficits in basal synaptic transmission in the hippocampus have been observed (Schindowski et al., 2006). At nine to ten months heterozygous mice exhibit altered paired pulse facilitation (PPF), a form of presynaptic short-term plasticity. They also have impaired maintenance of long-term depression compared with wild-type littermates (Van der Jeugd et al., 2011).

Modification Details

Transgene containing the cDNA of the 412 amino acid isoform of human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2 promotor.

Availability

Available through Luc Buée.

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

Plaques

Absent.

Tangles

Heterozygous animals develop tau pathology starting at 3-6 months. Pathology becomes more severe and widespread with age. Neurofibrillary tangle-like inclusions occur (Gallyas and MC1+) along with rare ghost tangles and paired helical filament-like structures (Schindowski et al., 2006).

Neuronal Loss

Loss of cells in the CA1 region of the hippocampus from 12 months as measured by DAPI staining and Nissl/cresyl-violet (Schindowski et al., 2006). Also, a significant reduction in the number of choline acetyltransferase (ChAT)-immunopositive cholinergic neurons in the medial septum has been reported (Belarbi et al., 2011).

Gliosis

Age-dependent increase in the number of GFAP+ astrocytes in the hippocampus (hilus, CA1, CA3), cerebral cortex, corpus callosum (Schindowski et al., 2006).

Changes in LTP/LTD

Altered paired pulse facilitation (PPF), a form of presynaptic short-term plasticity in 9-10 month old heterozygous animals: PPF increased at 10 ms. Also at this age, impaired maintenance of long term depression as compared with wild-type littermates (Van der Jeugd et al., 2011). Deficit in basal synaptic transmission in the hippocampus, but normal LTP (Schindowski et al., 2006).

Cognitive Impairment

Non-spatial memory affected as early as 6 months; spatial memory impaired only after 9 months (Van der Jeugd et al., 2013). Impaired appetitive responding (Lo et al., 2013).

Last Updated: 25 Nov 2019

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References

Paper Citations

  1. Schindowski K, Bretteville A, Leroy K, Bégard S, Brion JP, Hamdane M, Buée L. Alzheimer's disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am J Pathol. 2006 Aug;169(2):599-616. PubMed.
  2. Van der Jeugd A, Vermaercke B, Derisbourg M, Lo AC, Hamdane M, Blum D, Buée L, D'Hooge R. Progressive Age-Related Cognitive Decline in Tau Mice. J Alzheimers Dis. 2013 Jan 1;37(4):777-88. PubMed.
  3. Lo AC, Iscru E, Blum D, Tesseur I, Callaerts-Vegh Z, Buée L, De Strooper B, Balschun D, D'Hooge R. Amyloid and tau neuropathology differentially affect prefrontal synaptic plasticity and cognitive performance in mouse models of Alzheimer's disease. J Alzheimers Dis. 2013 Jan 1;37(1):109-25. PubMed.
  4. Van der Jeugd A, Ahmed T, Burnouf S, Belarbi K, Hamdame M, Grosjean ME, Humez S, Balschun D, Blum D, Buée L, D'Hooge R. Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission. Neurobiol Learn Mem. 2011 Mar;95(3):296-304. PubMed.

Other Citations

  1. Luc Buée

Further Reading

Papers

  1. Leboucher A, Laurent C, Fernandez-Gomez FJ, Burnouf S, Troquier L, Eddarkaoui S, Demeyer D, Caillierez R, Zommer N, Vallez E, Bantubungi K, Breton C, Pigny P, Buée-Scherrer V, Staels B, Hamdane M, Tailleux A, Buée L, Blum D. Detrimental Effects of Diet-Induced Obesity on τ Pathology Is Independent of Insulin Resistance in τ Transgenic Mice. Diabetes. 2012 Dec 18; PubMed.
  2. Burnouf S, Martire A, Derisbourg M, Laurent C, Belarbi K, Leboucher A, Fernandez-Gomez FJ, Troquier L, Eddarkaoui S, Grosjean ME, Demeyer D, Muhr-Tailleux A, Buisson A, Sergeant N, Hamdane M, Humez S, Popoli P, Buée L, Blum D. NMDA receptor dysfunction contributes to impaired brain-derived neurotrophic factor-induced facilitation of hippocampal synaptic transmission in a Tau transgenic model. Aging Cell. 2012 Oct 20; PubMed.
  3. Ando K, Dourlen P, Sambo AV, Bretteville A, Bélarbi K, Vingtdeux V, Eddarkaoui S, Drobecq H, Ghestem A, Bégard S, Demey-Thomas E, Melnyk P, Smet C, Lippens G, Maurage CA, Caillet-Boudin ML, Verdier Y, Vinh J, Landrieu I, Galas MC, Blum D, Hamdane M, Sergeant N, Buée L. Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker. Neurobiol Aging. 2012 Aug 25; PubMed.
  4. Troquier L, Caillierez M, Burnouf S, Fernandez-Gomez FJ, Grosjean MJ, Zommer N, Sergeant N, Schraen-Maschke S, Blum D, Buee L. Targeting phospho-Ser422 by active Tau immunotherapy in the THY-Tau22 mouse model: a suitable therapeutic approach. Curr Alzheimer Res. 2012 Jan 23; PubMed.
  5. Burnouf S, Belarbi K, Troquier L, Derisbourg M, Demeyer D, Leboucher A, Laurent C, Hamdane M, Buee L, Blum D. Hippocampal BDNF Expression in a Tau Transgenic Mouse Model. Curr Alzheimer Res. 2012 Jan 23; PubMed.
  6. Belarbi K, Burnouf S, Fernandez-Gomez FJ, Desmercières J, Troquier L, Brouillette J, Tsambou L, Grosjean ME, Caillierez R, Demeyer D, Hamdane M, Schindowski K, Blum D, Buée L. Loss of Medial Septum Cholinergic Neurons in THY-Tau22 Mouse Model: What Links with tau Pathology?. Curr Alzheimer Res. 2011 Sep 1;8(6):633-8. PubMed.
  7. Belarbi K, Burnouf S, Fernandez-Gomez FJ, Laurent C, Lestavel S, Figeac M, Sultan A, Troquier L, Leboucher A, Caillierez R, Grosjean ME, Demeyer D, Obriot H, Brion I, Barbot B, Galas MC, Staels B, Humez S, Sergeant N, Schraen-Maschke S, Muhr-Tailleux A, Hamdane M, Buée L, Blum D. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology. Neurobiol Dis. 2011 Aug;43(2):486-94. PubMed.
  8. Feuillette S, Deramecourt V, Laquerriere A, Duyckaerts C, Delisle MB, Maurage CA, Blum D, Buée L, Frébourg T, Campion D, Lecourtois M. Filamin-A and Myosin VI colocalize with fibrillary Tau protein in Alzheimer's disease and FTDP-17 brains. Brain Res. 2010 Jul 23;1345:182-9. PubMed.
  9. Belarbi K, Schindowski K, Burnouf S, Caillierez R, Grosjean ME, Demeyer D, Hamdane M, Sergeant N, Blum D, Buée L. Early Tau pathology involving the septo-hippocampal pathway in a Tau transgenic model: relevance to Alzheimer's disease. Curr Alzheimer Res. 2009 Apr;6(2):152-7. PubMed.
  10. Schindowski K, Belarbi K, Bretteville A, Ando K, Buée L. Neurogenesis and cell cycle-reactivated neuronal death during pathogenic tau aggregation. Genes Brain Behav. 2008 Feb;7 Suppl 1:92-100. PubMed.
  11. Laurent C, Eddarkaoui S, Derisbourg M, Leboucher A, Demeyer D, Carrier S, Schneider M, Hamdane M, Müller CE, Buée L, Blum D. Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology. Neurobiol Aging. 2014 Sep;35(9):2079-90. Epub 2014 Mar 29 PubMed.
  12. García-Gómez BE, Fernández-Gómez FJ, Muñoz-Delgado E, Buée L, Blum D, Vidal CJ. mRNA Levels of ACh-Related Enzymes in the Hippocampus of THY-Tau22 Mouse: A Model of Human Tauopathy with No Signs of Motor Disturbance. J Mol Neurosci. 2016 Apr;58(4):411-5. Epub 2015 Dec 23 PubMed.