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Experimental Genetics Group
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APP Transgenic Mice |
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APP-V717I transgenic mice: model for the amyloid pathology in AD
Our APP-V717I transgenic mice develop progressively
and robustly the typical amyloid pathology of AD, including
sequentially (i) intracellular amyloid peptides in a
vesicular appearance (age 3-9 months), (ii) diffuse plaques
(10-12 months) followed by (iii) senile amyloid plaques in
brain parenchym (12-15 months) and (iii) finally cerebrovascular
angiopathy (15-18 months) all further progressing
with age. Thereby, the APP-V717I mice are an excellent
model for the amyloid pathology in AD (Moechars
et al, 1999; Van Dorpe et al, 2000; Dewachter et al, 2000).
The APP-V717I transgenic mice serve as valuable preclinical
models for the amyloid pathology in AD and are
continously further characterized and exploited in many
academic collaborations and in projects with industrial
partners for biotechnological and pharmaceutical drug
development.
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Tau Transgenic Mice |
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Tau-P301L mice: tauopathy with hyperphosphorylation and aggregation of protein tau
Tau-P301L mice develop a moribund tauopathy with hyperphosphorylation and aggregation of protein tau, resulting in
neurofibrillary tangles (NFT) and neurodegeneration that is lethal around the age of 10-12 months (Terwel et al., 2005).
Tau-P301L mice thereby recapitulate the disease process of
FTD patients. Remarkably, at young age the tau-P301L mice
show better cognitive performance and stronger LTP than agematched
non-transgenic mice (Boekhoorn et al., 2006).
This is
construed to support the hypothesis that not the mutant itself,
but its (unknown) impact on the phosphorylation of mutant tau
with ageing causes the moribund tauopathy.
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APP x Tau Bi-genic Mice |
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Combined pathology in APP-V717I×Tau-P301L double transgenic mice
Combined amyloid and tau-pathology as a more complete
model for AD is obtained in APP-V717I×Tau-P301L
double transgenic mice. Offspring of sufficient old age (14-
18 months) contain amyloid and tau-pathology in all
important brain regions, including hippocampus and cortex.
Moreover, in addition to the combined pathology, synergistic
interaction was obvious by the more intense and more
widespread tauopathy in double transgenic mice, relative to
the parental strains. Brain regions that are typically subject
to pathology in AD, i.e. entorhinal cortex, hippocampus
and neocortex, were loaded with amyloid and NFT in aged
APP-V717I×Tau-P301L double transgenic mice.
Ongoing
analysis concerns the earliest symptoms of cognitive, social
and sensori-motor behavior, to define the exact nature of
the synergism in pathology and its repercussions on, and correlation with, the clinical symptoms (Muyllaert et al, 2008; Terwel et al, 2008; and unpublished data).
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Overview LEGT_EGG mice |
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List of LEGT_EGG transgenic mice with most relevant references.
| APP-V717I |
Moechars D et al., 1999 |
| Van Dorpe et al., 2000 |
| Dewachter I et al., 2000 |
| Willem M et al., 2004 |
| Etcheberrigaray et al., 2004 |
| Postina R et al., 2004 |
| Vanhoutte G et al., 2005 |
| Van Dooren T et al., 2005 |
| PS1-A246E |
Dewachter I et al., 2000 |
| Van Dorpe et al., 2000 |
| Schneider et al., 2001 |
| PS1(-/-) |
De Strooper B et al., 1998 |
Dewachter I et al., 2002
(conditional KO) |
| tau-4R |
Spittaels K et al., 1999 |
| Terwel D et al., 2005 |
| Vandebroek T et al., 2005 |
| tau-P301L |
Terwel D et al., 2005 |
| Boekhoorn K et al., 2006 |
| bigenic biAT & biGT |
Terwel et al., 2008 |
| Muyllaert et al., 2008 |
| Muyllaert et al, 2006 |
| GSK-3ß |
Spittaels K et al., 2000 |
| Tilleman K et al., 2002 |
| Terwel D et al., 2002 |
| Spittaels K et al., 2002 |
| cdk5/p35/p25 |
Van Den Haute C et al., 2001 |
| Muyllaert D. et al., 2008 |
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