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Title: Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

Abstract

We report on a behavioral screening test battery 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 employed 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 hyper-locomotion, the other hypo-locomotion), 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.

Authors:
 [1];  [1];  [2];  [3];  [3];  [4]
  1. University of Memphis
  2. Vanderbilt University and Veterans Administration, Nashville, TN
  3. ORNL
  4. University of Tennessee Health Science Center, Memphis
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mouse Genetics Research Facility
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
958787
DOE Contract Number:  
DE-AC05-00OR22725
Resource Type:
Journal Article
Resource Relation:
Journal Name: Mammalian Genome; Journal Volume: 18; Journal Issue: 8
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; CENTRAL NERVOUS SYSTEM; GENES; GENETIC MAPPING; LEARNING; MICE; MUTAGENESIS; MUTANTS; PERFORMANCE; SCREENS; TARGETS; ENU; Behavior; Mutagenesis; Mutant

Citation Formats

Cook, Melloni N., Dunning, Jonathan P, Wiley, Ronald G, Chesler, Elissa J, Johnson, Dabney K, and Goldowitz, Daniel. Neurobehavioral Mutants Identified in an ENU Mutagenesis Project. United States: N. p., 2007. Web. doi:10.1007/s00335-007-9035-3.
Cook, Melloni N., Dunning, Jonathan P, Wiley, Ronald G, Chesler, Elissa J, Johnson, Dabney K, & Goldowitz, Daniel. Neurobehavioral Mutants Identified in an ENU Mutagenesis Project. United States. doi:10.1007/s00335-007-9035-3.
Cook, Melloni N., Dunning, Jonathan P, Wiley, Ronald G, Chesler, Elissa J, Johnson, Dabney K, and Goldowitz, Daniel. Mon . "Neurobehavioral Mutants Identified in an ENU Mutagenesis Project". United States. doi:10.1007/s00335-007-9035-3.
@article{osti_958787,
title = {Neurobehavioral Mutants Identified in an ENU Mutagenesis Project},
author = {Cook, Melloni N. and Dunning, Jonathan P and Wiley, Ronald G and Chesler, Elissa J and Johnson, Dabney K and Goldowitz, Daniel},
abstractNote = {We report on a behavioral screening test battery 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 employed 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 hyper-locomotion, the other hypo-locomotion), 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.},
doi = {10.1007/s00335-007-9035-3},
journal = {Mammalian Genome},
number = 8,
volume = 18,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}