Neurobehavioral mutants identified in an ENU-mutagenesis project
- 153 Downloads
We report on a battery of behavioral screening tests that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU-mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and used a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open-field mutants (one displaying hyperlocomotion, the other hypolocomotion), four tail-suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsiveness to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning-and-memory mutant (displaying reduced response to the conditioned stimulus). These findings highlight the utility of a set of behavioral tasks used in a high-throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.
KeywordsConditioned Stimulus Open Field Fear Conditioning Startle Response Prepulse Inhibition
This work was supported by NIMH grant U01-MH61971 to DG with subcontract to MNC and 1 U01 AA013503 to DG. The authors gratefully acknowledge the important contributions of Gene Rinchik, Karen Goss, Ginger Shaw, Jason Spence, Jennifer Manrod, Eric Baker, Barbara Jackson, Leslie Galloway, Jody Cockroft, Andy Bush, Jay Snoddy, Lu Lu, Douglas Swanson, and all others involved at different levels and phases of this project. The authors also thank Drs. Howard Gershenfeld and Richard Paylor for their helpful advice and direction in the development and implementation of our behavioral screen.
- Chesler EJ, Wilson SG, Lariviere WR, Rodriguez-Zas SL, Mogil JS (2002) Identification and ranking of genetic and laboratory environment factors influencing a behavioral trait, thermal nociception, via computational analysis of a large data archive. Neurosci Biobehav Rev 26(8):907–923PubMedCrossRefGoogle Scholar
- Hamre KM, Goldowitz D, Wilkinson S, Matthew DB (2007) Screening for ENU-induced mutations in mouse that result in aberrant ethanol-related phenotypes. Behav NeurosciGoogle Scholar
- Rousseeuw P, Leroy A (1987) Robust Regression and Outlier Detection (New York: Wiley and Sons)Google Scholar
- Swanson D, Hamre K, et al. (2003) Robust analysis of quantitative mutant phenotypes: implications for neuro-behavioral mutagenesis. Presented at the meeting of the Society for Neuroscience, New Orleans, LA, Program No. 864.13, 8–12 Nov 2003Google Scholar