Brain-wide mapping of transgene expression in mouse models of neurodegenerative disease
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AbstractGenetically modified mice are important tools in the effort to understand neurodegenerative conditions and identify potential therapeutic targets. A wide range of transgenic mouse models have been developed, but since each model only replicates certain aspects of the human disease, it is essential to choose the most appropriate model for a particular study. Finding the most suitable model requires careful assessment of phenotype data, including empirical descriptions of the level and anatomical location of transgene expression. Lillehaug and colleagues have utilized tools and infrastructure developed in context of the EU Human Brain Project to establish, optimize and test workflows for analysis of morphological features in transgenic mouse models for neurodegenerative disease. They have demonstrated how the anatomical location and variance of transgene expression can be quantitatively assessed and how comparison of cellular labeling in mouse brains can be improved by spatially relating microscopic images to a three-dimensional mouse brain atlas framework. Finally, they have demonstrated how large collections of histological image data can be publicly shared in accordance with the F.A.I.R. principles (Wilkinson et al. 2016), ensuring that the data are Findable, Accessible, Interoperable, and Reusable.
List of papers
|Paper I. Brainwide distribution and variance of amyloid-beta deposits in tg-ArcSwe mice. Lillehaug S, Syverstad GH, Nilsson LN, Bjaalie JG, Leergaard TB, Torp R. Neurobiology of Aging 35:556-64, 2014. DOI: 10.1016/j.neurobiolaging.2013.09.013 PMID: 24126157. The article is included in the thesis. Also available at https://doi.org/10.1016/j.neurobiolaging.2013.09.013|
|Paper II. Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex. Yetman MJ, Lillehaug S, Bjaalie JG, Leergaard TB, Jankowsky JL. Brain Structure and Function 221:2231-49, 2016. DOI: 10.1007/s00429-015-1040-9. PMID: 25869275. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1007/s00429-015-1040-9|
|Paper III. Brain-wide distribution of reporter expression in five transgenic tetracycline-transactivator mouse lines. Lillehaug S, Yetman MJ, Puchades MA, Checinska MM, Kleven H, Jankowsky JL, Bjaalie JG, Leergaard TB. Scientific Data 6:190028, 2019. DOI: 10.1038/sdata.2019.28. PMID: 30806643. The article is included in the thesis. Also available in DUO: http://urn.nb.no/URN:NBN:no-75741|