The Jackson Laboratory

Pleiades Promoter Project mice shine at The Jackson Laboratory

JAX^® NOTES Issue 513, Spring 2009

In Greek mythology, the Pleiades cluster represents the seven daughters of the Titan god, Atlas. Analogously, the Pleiades Promoter Project is a "daughter" of the Mouse Atlas Project, a scientific resource that provides expression maps of approximately 20,000 genes in the mouse. Led by University of British Columbia and former Jackson Laboratory scientist, Dr. Elizabeth Simpson, the Pleiades Promoter Project is a $10.2 million, four-year, Genome Canada research initiative to build neurogenomic tools to advance research and gene-driven therapies for brain and eye disorders. Among these tools will be a series of mutant mouse strains genetically engineered with human promoters that will drive the expression of reporter molecules (either fluorescent or stainable proteins) where genes are expressed in regions of therapeutic interest in the mouse brain or eye. Approximately 70 mouse lines from the project will be distributed by The Jackson Laboratory.

Expression from the Ple111 MiniPromoter shows specific staining in a subpopulation of neurons in the hypothalamus A) and B) detail of region boxed in A. MiniPromoter Ple111 is based on the human HCRT gene. Detection of EGFP reporter was performed with anti-EGFP immunocytochemistry using DAB to give a brown reaction product. Scale Bar is A) 500 µm and B) 50 µm.

Each Pleiades mouse line will be genetically engineered to contain a unique human promoter-reporter (LacZ, EGFP or EGFPcre) construct knocked into the hypoxanthine guanine phosphoribosyl transferase 1 (Hprt1) locus. The human promoters were chosen only if they controlled genes richly expressed in the target tissues. They were identified by analyzing data from the Allen Brain Atlas and by using a variation of the serial analysis of gene expression technique (LongSAGE) (D'souza et al. 2008). Because regional expression patterns within tissues tend to be conserved between orthologous mouse and human genes, characterizing gene expression in the Pleiades mice will help researchers better understand the expression patterns of human promoters and improve gene-based therapies for diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, multiple sclerosis, spinocerebellar ataxia, depression, autism and cancer.

You can express interest in the first two mouse strains from the Pleiades Promoter Project:

B6.129P2-Hprt1^{tm4(GFAP-EGFP)Ems}/J (008706)

B6.129P2-Hprt1^{tm8(OLIG1-EGFP)Ems}/J (008708)

Reference

D'souza CA, Chopra V, Varhol R, Xie YY, Bohacec S, Zhao Y, Lee LL, Bilenky M, Portales-Casamar E, He A, Wasserman WW, Goldowitz D, Marra MA, Holt RA, Simpson EM, Jones SJ. 2008. Identification of a set of genes showing regionally enriched expression in the mouse brain. BMC Neurosci 9:66.