Development of Recombinase-Expressing (“Driver”) Mouse Lines for Studying the Nervous System
Concept Clearance — March 2005
Presenter
Andrea Beckel-Mitchener, Ph.D.
Chief, Functional Neurogenomics Program
Molecular, Cellular, and Genomic Research Branch
Division of Neuroscience and Basic Behavioral Science, NIMH
Description
The Neuroscience Blueprint provides a framework to enhance cooperative activities among fifteen NIH Institutes and Centers that support research on the nervous system. By pooling resources and expertise and prospectively coordinating initiatives, the Blueprint can take advantage of economies of scale, confront challenges too large for any single Institute or Center, and develop enabling research tools and resources that will serve the neuroscience community broadly. The NIH Office of the Director has provided funding for the Blueprint project described here, and NIMH has been designated as the lead Institute to coordinate the effort on behalf of all Blueprint participants.
The use of transgenic mice is widely recognized as a critical element in studying the development and function of the nervous system as well as providing an approach to model aspects of various disorders. Many of the mouse models currently available are strict null mutants, which can limit their utility such as in the case of knockout lethality. Genetic knockouts that are spatially and/or temporally restricted may circumvent lethality issues and can provide for a more detailed analysis of particular gene products in specified regions or in critical developmental periods. Restricted gene expression is generally achieved by crossing a “driver” line (mice containing a recombinase enzyme under the control of promoter elements that specify its expression pattern), with mice containing a “conditional ready” allele that has sequence elements responsive to the recombinase within the gene of interest. Currently, only very few useful driver lines exist for studies of the nervous system. This initiative will support the construction and validation of cell- and/or regionally-specific driver lines that can be crossed with appropriate “conditional ready” mice to drive predictably patterned gene deletions in order to facilitate neurobiology research. The panel of driver lines created will be a novel and powerful resource that will promote additional functional studies. This multi-institute endeavor is coordinated with, and complementary to, ongoing efforts from the Knockout Mouse Project (KOMP) as well as those occurring in the European Community. In accordance with Blueprint objectives, it is expected that the driver lines developed and made available to the scientific community through this initiative will cover a variety of different regions within the nervous system with defined expression patterns across the lifespan.
Note: The activities of the Neuroscience Blueprint (including the FY06 Neuromouse initiative) were presented to the National Advisory Mental Health Council as part of the public presentations in May 2005. The Neuromouse initiative is partially derived from discussions at an NIH workshop on the development and utility of knockout mouse resources held in March 2005 and the concept has subsequently been discussed at various scientific meetings.
Comments
Submit comments to Jean Noronha at jnoronha@mail.nih.gov.
