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Printable Handouts
Navigable Slide Index
- Introduction
- Introduction and scope
- Animal models and neurodegenerative diseases
- The challenge of reproducibility
- Tauopathies
- A spectrum of aetiologies for FTD
- Tau transgenics
- How Tg mouse lines are made, propagated
- A generalized transgene construct
- There is not a unique tau protein sequence
- Tau is subject to post-translational modifications
- Encoding variant forms of tau: alternative cDNA
- Variant forms of tau: phosphomimetic alleles
- Encoding variant forms of tau
- Delivery of purified DNA into germline cells
- DNA integration and transgene 'copy-number'
- Breeding founders to make batches of Tg offspring
- Transgene integration sites, copy-number and expression levels
- Half-genomic' vectors derived from a mouse PrP cosmid
- Endogenous promoter sequence
- Using mutant tau sequences
- rTg4510 mice: tet-off system using doxycycline
- Rat Tg lines with tau pathology
- Delivering transgenes with viral vectors
- Endpoints attained in single-Tg models
- Limitations relating to tau Tg mice
- Variations in phenotypic penetrance
- A question of ageing
- Comparative ageing in animal models
- Transgene expression, pathology and life stages
- Human tau interactions with endogenous mouse tau
- Beyond tau Tg mice - other types of models
- Idiopathic (sporadic) forms of disease
- Polygenic approaches to sporadic tauopathies
- Prion effects
- Delivery of pathogenic protein; a different type of vectoring
- CTE and TBI in humans
- Diversity in misfolded proteins & phenotypic outcomes
- Using models to advance understanding
- Considerations on closing: other types of models
- Considerations on closing
Topics Covered
- General considerations about animal models
- Genetic and idiopathic tauopathies
- Transgenic mice
- Principles and practice for tau animal models
- Limitations of Tg mice
- Alternative approaches for modeling tauopathies
- Future prospects for animal models of tauopathy
Links
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External Links
Talk Citation
Westaway, D. (2021, September 30). Animal models of tauopathy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/CGLN8981.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. David Westaway has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neuroscience
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is David Westaway and I'm with the Center for Prions and
Protein Folding Diseases at the University of Alberta in Edmonton, Alberta.
This topic concerns animal models of tauopathy.
0:15
In terms of scope,
we are going to consider the following items.
There are procedural considerations regarding animal models,
including the broader contexts for translational research.
I will describe some properties of tauopathies
including the genetic and idiopathic forms.
I will provide a brief reprise of key facts about
transgenic mice and how they are used intensely in this field.
Some of the ways in which they are constructed affect
how they might be used in a research context.
There are also models beyond transgenic mice to be considered.
These may transcend some of the technical challenges of transgenic mice.
I'll discuss briefly some of those alternative approaches to modeling.
Lastly, I'll make
some concluding remarks with prospects as to where this discipline might be going.
1:07
In a broad picture considering animal models and neurodegenerative diseases,
a number of goals can be considered.
Models can be used for testing candidates therapies,
for validating new biomarkers,
potentially for developing imaging reactions,
and for performing toxicity studies on new candidates therapeutics.
In the course of carrying out the types of studies mentioned above,
animal models can, themselves, tell us about missing or unsuspected aspects of biology.
These models can sometimes make us realize that our knowledge of
pathogenesis is incomplete, or in some cases is actually incorrect.
By looking carefully at these models,
we can arrive at a new and better understanding.
At the practical level to arrive at animal models,
what we're doing is employing techniques to deliver genes or
pathogenesis-prone proteins into laboratory animals.