Authors:
Elodie Portales-Casamar, Douglas J. Swanson, Li Liu, Charles N. de Leeuw, Kathleen G. Banks, Shannan J. Ho Sui, Debra L. Fulton, Johar Ali, Mahsa Amirabbasi, David J. Arenillas, Nazar Babyak, Sonia F. Black, Russell J. Bonagura, Erich Brauer, Tara R. Candido, Mauro Castellarin, Jing Chen, Ying Chen, Jason C. Y. Cheng, Vik Chopra, T. Roderick Docking, Lisa Dreolini, Cletus A. D'Souza, Erin K. Flynn, Randy Glenn, Kristi Hatakka, Taryn G. Hearty, Behzad Imanian, Steven Jiang, Shadi Khorasan-zadeh, Ivana Komljenovic, Stéphanie Laprise, Nancy Y. Liao, Jonathan S. Lim, Stuart Lithwick, Flora Liu, Jun Liu, Meifen Lu, Melissa McConechy, Andrea J. McLeod, Marko Milisavljevic, Jacek Mis, Katie O'Connor, Betty Palma, Diana L. Palmquist, Jean-François Schmouth, Magdalena I. Swanson, Bonny Tam, Amy Ticoll, Jenna L. Turner, Richard Varhol, Jenny Vermeulen, Russell F. Watkins, Gary Wilson, Bibiana K. Y. Wong, Siaw H. Wong, Tony Y. T. Wong, George S. Yang, Athena R. Ypsilanti, Steven J. M. Jones, Robert A. Holt, Daniel Goldowitz, Wyeth W. Wasserman, and Elizabeth M. Simpson
Summary:
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.
Source:
The Proceedings of the National Academy of Sciences of the United States of America; Vol. 107, No. 38, 16589-16594 (09/21/10)