A regulatory toolbox of MiniPromoters to drive selective expression in the brain

Elodie Portales-Casamar, Douglas Swanson, Li Liu, Charles de Leeuw, Kathleen Banks, Shannan Ho Sui, Debra Fulton, Johar Ali, Mihsa Amirabbassi, David Arenillas, Nazar Babyak, Sonja Black, Russell Bonaguro, Erich Brauer, Tara Candido, Mauro Castellarin, Jing Chen, Ying Chen, Jason Cheng, Vik ChopraT Docking, Lisa Dreolini, Cletus D'Souza, Erin Flynn, Randy Glenn, Kristi Hatakka, Taryn Hearty, Behzad Imanian, Steven Jiang, Shadi Khorasan-zadeh, Ivana Komljenovic, Stephanie Laprise, Nancy Liao, Jonathan Lim, Stuart Lithwick, Flora Liu, Jun Liu, Meifen Lu, Melissa McConechy, Andrea McLeod, Marko Milisavljevic, Jacek Mis, Katie O'Connor, Betty Palma, Diana Palmquist, Jean-Francois Schmouth, Magdalena Swanson, Bonny Tam, Amy Ticoll, Jenna Turner, Richard Varhol, Jenny Vermeulen, Russell Watkins, Gary Wilson, Bibiana Wong, Siaw Wong, Tony Wong, George Yang, Athena Ypsilanti, Steven Jones, Robert Holt, Daniel Goldowitz, Wyeth Wasserman, Elizabeth Simpson

Research output: Contribution to journalArticleResearchpeer-review

55 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)16589 - 16594
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number38
DOIs
Publication statusPublished - 2010
Externally publishedYes

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