Trans-NIH Mouse Initiative


Pleiades Promoter Project

Gene therapy is the most promising new frontier in medical therapeutic intervention. Worldwide, numerous gene therapy trials have been conducted, some with devastating consequences, but some with tantalizing successes. From these experiences, several themes to increase safety have emerged: 1) more clinically relevant basic research is needed; 2) promoters should have specificity to reduce inappropriate expression; and 3) random insertion into the genome is undesirable due to possible mutagenesis or insertion-site effects. The Pleiades Promoter Project will address all three. The end goal of this project is to generate 160 fully characterized, human DNA MiniPromoters (less than 4 kb) to drive gene expression in defined brain regions of therapeutic interest for diseases such as Alzheimer, Parkinson, Huntington, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Spinocerebellar Ataxia, Depression, Autism, and Cancer. Intermediate deliverables include 205 embryonic stem cell lines carrying human Maxi (contained in BACs) or Mini (contained in plasmids) Promoters designed to be modified for delivery of gene products in the mouse brain; 205 mouse strains expressing EGFP or EGFPcre recombinase in the brain; 45 fully characterized human DNA MaxiPromoters; and novel software for MiniPromoter design and construction. Seventeen brain regions of therapeutic interest have been isolated from mouse by laser capture microscopy (LCM) and libraries have been prepared by using, for the first time, a combination of Serial Analysis of Gene Expression (SAGE)-Lite and LongSAGE technologies.

Project Website:

Russell F.Watkins, Ph.D.
Project Manager, Pleiades Promoter Project Centre for Molecular Medicine and Therapeutics 950 West 28th Avenue Vancouver, B.C.
V5Z 4H4
Tel: (604) 875-2000 x 7100
Fax: (604) 875-3819