Using non-invasive in vivo imaging to address the 3Rs in high-throughput mouse phenotyping

In the wake of the first draft of the full mouse genome sequence, large-scale mutagenesis programmes are underway that will produce mice with gene knockouts/point mutations for each of the approximately 25,000 genes in the mouse genome. Analysis of these mice in coming years will give new insights into the genetic basis of human disease and biology, as novel genes are identified that impact upon mammalian physiology and morphology. This studentship will develop non-invasive imaging of live mice to reduce the numbers of mice generated in high-throughput mutagenesis programs and start to refine experimental strategies for working with mouse models. We will use non-invasive in-vivo magnetic resonance imaging (MRI), to assess if this imaging technology can help us understand the function of genes within the brain, which will enable us remove major "bottlenecks" in the development of new diagnosis tests for genetic disease and human gene therapies.

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Powell NM et al. (2016). Fully-Automated μMRI Morphometric Phenotyping of the Tc1 Mouse Model of Down Syndrome. PLoS One 11(9):e0162974. doi: 10.1371/journal.pone.0162974

Wells JA et al. (2015). In vivo imaging of tau pathology using multi-parametric quantitative MRI. NeuroImage 111:369-78. doi: 10.1016/j.neuroimage.2015.02.023

Wells JA et al. (2015). Increased cerebral vascular reactivity in the tau expressing rTg4510 mouse: evidence against the role of tau pathology to impair vascular health in Alzheimer's disease. Journal of Cerebral Blood Flow and Metabolism 35(3):359-62. doi: 10.1038/jcbfm.2014.224

O'Callaghan J et al. (2014). Is your system calibrated? MRI gradient system calibration for pre-clinical, high-resolution imaging. PLoS One 9(5):e96568. doi: 10.1371/journal.pone.0096568

Ma D et al. (2014). Automatic structural parcellation of mouse brain MRI using multi-atlas label fusion. PLoS One 9(1):e86576. doi: 10.1371/journal.pone.0086576

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PhD Studentship

Status

Closed

Principal investigator

Dr Mark Lythgoe

Institution

University College London

Co-Investigator

Professor Elizabeth Fisher
Dr Sebastien Ourselin
Dr Abraham Acevedo

Grant reference number

NC/K500276/1

Award date

Sep 2011 - Sep 2015

Grant amount

£120,000

'R'

Reduction

Keywords

MRI