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RNA Interferes With Parkinson Gene DOI: 10.1038/nm964 (http://dx.doi.org/10.1038/nm964) Researchers have created a mouse model of Parkinson disease using a technique called viral-mediated RNA interference (RNAi), according to a report in the December issue of Nature Medicine. Ralph DiLeone and colleagues used the adeno-associated virus to carry folded pieces of double-stranded RNA--called short hairpin RNA--into the cells in specific areas of adult mouse brains. The RNA decreased the expression of tyrosine hydroxylase (TH), an enzyme involved in producing the neurotransmitter dopamine. The resulting motor defects in the mice resembled symptoms of Parkinson disease. The traditional genetic 'knockout' technique, which completely eliminates TH, results in mice that die within three weeks after birth. The researchers say viral-mediated RNAi could be used in other species to quickly generate disease models to identify disease-causing genes and test new therapies. SOURCE: Newswise http://www.newswise.com/p/articles/view/502096/ Local Gene Knockdown In The Brain Using Viral-Mediated RNA Interference Jonathan D Hommel, Robert M Sears, Dan Georgescu, Diana L Simmons & Ralph J DiLeone Nature Medicine Published online: 23 November 2003, doi:10.1038/nm964 December 2003 Volume 9 Number 12 pp 1539 - 1544 Abstract: Conditional mutant techniques that allow spatial and temporal control over gene expression can be used to create mice with restricted genetic modifications. These mice serve as powerful disease models in which gene function in adult tissues can be specifically dissected. Current strategies for conditional genetic manipulation are inefficient, however, and often lack sufficient spatial control. Here we use viral-mediated RNA interference (RNAi) to generate a specific knockdown of Th, the gene encoding the dopamine synthesis enzyme tyrosine hydroxylase, within midbrain neurons of adult mice. This localized gene knockdown resulted in behavioral changes, including a motor performance deficit and reduced response to a psychostimulant. These results underscore the potential of using viral-mediated RNAi for the rapid production and testing of new genetic disease models. Similar strategies may be used in other model species, and may ultimately find applications in human gene therapy. Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75390–9070, USA Correspondence should be addressed to R J DiLeone. e-mail: [log in to unmask] SOURCE: Nature Medicine http://tinyurl.com/x99x * * * ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn