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Mouse Models of Neurodegenerative Diseases: Criteria and General Methodology

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Mouse Models for Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 602))

Abstract

The major symptom of Alzheimer’s disease is rapidly progressing dementia, coinciding with the formation of amyloid and tau deposits in the central nervous system, and neuronal death. At present familial cases of dementias provide the most promising foundation for modelling neurodegeneration. We describe the mnemonic and other major behavioral symptoms of tauopathies, briefly outline the genetics underlying familiar cases and discuss the arising implications for modelling the disease in mostly transgenic mouse lines. We then depict to what degree the most recent mouse models replicate pathological and cognitive characteristics observed in patients.

There is no universally valid behavioral test battery to evaluate mouse models. The selection of individual tests depends on the behavioral and/or memory system in focus, the type of a model and how well it replicates the pathology of a disease and the amount of control over the genetic background of the mouse model. However it is possible to provide guidelines and criteria for modelling the neurodegeneration, setting up the experiments and choosing relevant tests. One should not adopt a “one (trans)gene, one disease” interpretation, but should try to understand how the mouse genome copes with the protein expression of the transgene in question. Further, it is not possible to recommend some mouse models over others since each model is valuable within its own constraints, and the way experiments are performed often reflects the idiosyncratic reality of specific laboratories. Our purpose is to improve bridging molecular and behavioural approaches in translational research.

A man is but what he knoweth ,

Sir Francis Bacon (1).

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

β-amyloid peptide

FAD:

amilial Alzheimer’s disease

FTD:

fronto-temporal dementia

FTDP-17:

fronto-temporal dementia with parkinsonism linked to chromosome 17

GLM:

general linear model

MAPT:

microtubule-associated protein Tau

MCI:

mild cognitive impairment

NFT:

neurofibrillary tangles

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Acknowledgements

We would like to thank Amanda Hanna, Heather Melrose, Douglas Wahlsten, and Alexander Gaukhman for valuable comments on earlier drafts of the manuscript.

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Authors and Affiliations

  1. Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA

    Christopher Janus

  2. Division of Neuroanatomy and Behavior, Institute of Anatomy, University of Zürich, Zürich, Switzerland

    Hans Welzl

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  1. Christopher Janus
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Correspondence to Christopher Janus .

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Editors and Affiliations

  1. The Jackson Laboratory, Main Street 600, Bar Harbor, 04609, Maine, USA

    Gabriele Proetzel

  2. Jackson Laboratory, Main Street 600, Bar Harbor, 04609, USA

    Michael V. Wiles

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Janus, C., Welzl, H. (2010). Mouse Models of Neurodegenerative Diseases: Criteria and General Methodology. In: Proetzel, G., Wiles, M. (eds) Mouse Models for Drug Discovery. Methods in Molecular Biology, vol 602. Humana Press. https://doi.org/10.1007/978-1-60761-058-8_19

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