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Center for Functional Genomics at Northwestern University

National Institutes of Health

The NIH Neurogenomics Project at Northwestern University

Directed by Dr. Joseph Takahashi, the NIH Neurogenomics Project at Northwestern University is dedicated to furthering functional genomics research, by utilizing phenotype-driven, or forward genetics, techniques to identify genes.

Background

The National Institutes of Health (NIH) have recognized the importance of phenotype-driven approaches in bridging the gap between gene identification and understanding gene function. Knowledge of the genetics of nervous system function and regulation of behavior will lead to improved understanding of normal and abnormal brain function and behavior, enhanced diagnostics, and more effective therapeutics. The NIH Neurogenomics Project at Northwestern University is one of three Centers funded by NIH to use forward genetic strategies to identify genes involved in nervous system function and behavior.

Objective

Established in 2001, the overall objective has been to use ENU-mutagenized C57BL/6J mice to identify neurobehavioral mutations in five domains. The project uses a three-generation breeding scheme to produce homozygous mutants to recover both recessive and dominant mutations. Phenotypic screens focus on five primary domains: neuroendocrine and behavioral responses to stress, learning and memory, psychostimulant response, vision, and circadian rhythm.

Goals

  • Phenotypically screen 10,000 ENU-mutagenized C57BL/6J, G3 mice/year.
  • Assess heritability and mode of inheritance of traits through breeding.
  • Genetically map high-priority mutations.
  • Distribute data and information regarding the mice, as well as the mutant mice, to the greater scientific community through Neuromice.org.

Funding

The NIH Neurogenomics Project at Northwestern University is supported by grants from the National Institute of Mental Health, the National Institute on Drug Abuse, the National Institute on Deafness and Other Communicative Disorders, the National Institute on Aging, the National Eye Institute, and the National Institute on Alcohol Abuse and Alcoholism.

Location

The NIH Neurogenomics Project is part of The Center for Functional Genomics at Northwestern University, near Chicago, Illinois.

Collaboration

The NIH Neurogenomics Project collaborates with the Neuroscience Mutagenesis Facility at The Jackson Laboratory and the Neuromutagenesis Project of the Tennessee Mouse Genome Consortium to form Neuromice.org.

Publications

  • Clark, A.T., D. Goldowitz, J.S. Takahashi, M.H. Vitaterna, S.M. Siepka, L.L. Peters, W.N. Frankel, G.A. Carlson, J. Rossant, J. Nadeu, and M.J. Justice. 2004. Implementing large-scale ENU mutagenesis screens in North America. Genetica 122:51-64.
  • Pinto, L.H., M.H. Vitaterna, K. Shimomura, S. Lumayag, M. Baker, D. Fenner, R.A. Mullins, V. Sheffield, E. Stone, E. Heffron, J. S. Takahashi. 2004. Initial Results from Screening over 9,000 Chemically-Mutagenized Mice for Defects in the Electroretinogram and Appearance of the Fundus. Vis Res 44:3335-45.
  • Goldowitz D, WN Frankel, JS Takahashi, MH Vitaterna, C Bult, WA Kibbe, J Snoddy, Y Li, S Pretel, J Yates, DJ Swanson. 2004. Large-scale mutagenesis of the mouse to understand the genetic bases of nervous system structure and function. Molecular Brain Research 132:105-115.
  • Pinto, L.H. Vitaterna, M. H., Shimomura, K., Siepka, S. M., Blondell, E. M., Lumayag, S.L., Omura, C., Andrews, A.W., Baker, M., Invergo, B. M., Heffron, E., Mullins, R.F., Sheffield, V.C., Stone, E.M., and Takahashi, J.S. 2005. Generation, Characterization and Molecular Cloning of the Noerg-1 Mutation in the Mouse. Visual Neuroscience (in press).
  • Bult C, Kibbe WA, Snoddy J, Vitaterna M, Swanson D, Pretel S, Li Y, Hohman MM, Rinchik E, Takahashi JS, Frankel WN, Goldowitz D. 2004. A genome end-game: understanding gene function in the nervous system. Nature Neuroscience May 7(5):484-5.
  • Siepka SM, Takahashi JS. 2005. Methods to record circadian rhythm wheel running activity in mice. Methods in Enzymology 393:230-9.
  • Siepka SM, Takahashi JS. 2005. Forward genetic screens to identify circadian rhythm mutants in mice. Methods in Enzymology 393:219-29.