Research Models

Selected Results

2 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathology Behavior/Cognition Other Phenotype Availability Primary Paper Visualization
Mouse Models (2)
line 13 C57BL/6 x DBA/2F1, crossed with DBA MAPT MAPT L266V, MAPT G272V Transgene expressing human 3R tau bearing the L266V and G272V mutations under the neuronal mThy-1 promoter. MAPT: Transgenic Frontotemporal Dementia, Pick's disease, Alzheimer's Disease Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology. Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test. Increased anxiety. Unknown Rockenstein et al., 2015 Yes
Tau22 C57BL6/CBA; backcrossed to C57BL6 MAPT MAPT G272V, MAPT P301S 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. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis. Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity. Fertile with normal frequency and size of litters. Stably transmits the transgene to offspring. Deficits in hippocampal synaptic transmission. Available through Luc Buée Schindowski et al., 2006 Yes

2 Visualizations

AD-related Research Models

Phenotypes Examined

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

When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.

mThy-1 3R Tau (line 13)

Observed
  1. X
    Tangles at 34

    Pick-body like inclusions of aggregated tau appeared in the hippocampus and cortex by 8-10 months. Inclusions were positive for Bielchowsky silver stain but negative for Gallyas-silver stain and Thioflavin-S.

  2. X
    Neuronal Loss at 34

    Neuronal loss occurred by 8-10 months as evidenced by decreased NeuN staining in the dentate gyrus and CA3 regions of the hippocampus. Neocortical volume also decreased.

  3. X
    Gliosis at 35

    Astrogliosis was seen by 8-10 months in the neocortex and hippocampus. Some GFAP+ astrocytes also contained 3R tau.

  4. X
    Cognitive Impairment at 26

    By 6-8 months memory impairment was evident as a failure to habituate to a novel environment. This deficit was not present at 3-4 months. At 8-10 months, transgenics also took longer than wild-type mice to find the hidden platform in the Morris water maze.

Absent
  • Plaques at

    Absent.

No Data
  • Synaptic Loss at

    Synapto-dendritic damage manifested as reduced dendritic density, reduced MAP2 immunoreactivity, and accumulation of 3R tau in dendrites.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT L266V, MAPT G272V MAPT: Transgenic Frontotemporal Dementia, Pick's disease, Alzheimer's Disease

Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology.

Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test.

expand

THY-Tau22

Observed
  1. X
    Tangles at 13

    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).

  2. X
    Neuronal Loss at 52

    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).

  3. X
    Gliosis at 13

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

  4. X
    Changes in LTP/LTD at 39

    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).

  5. X
    Cognitive Impairment at 26

    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).

Absent
  • Plaques at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT G272V, MAPT P301S MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis.

Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity.

expand