Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 38, Pages 16589-16594Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1009158107
Keywords
knockin mice; neuroscience; promoter design; selective expression; transcription
Categories
Funding
- Genome Canada
- Genome British Columbia
- Glaxo Smith Kline RD Ltd.
- BC Mental Health and Addiction Services
- Child and Family Research Institute
- University of British Columbia (UBC)
- UBC Office of the Vice President Research
- Canadian Research Chairs
- Canadian Institutes of Health Research
- Michael Smith Foundation
- Natural Sciences and Engineering Research Council of Canada
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The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination knockins in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5 ' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type-specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.
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