This is a new core that was developed to meet the need for behavioral and histological screening of new mouse mutants produced by Core C for project 1,2,3,5,6 and 7 of this program of projects proposal. Having identified several genes potentially involved in the neural and behavior phenotype of DS, the projects proposed to produce genetically manipulated mice to determine the roles of individual genes or gene regions in the phenotype of DS. These models will include a) segmental trisomic mice; b) transgenic mice; c) knock-out mice d) Cre-Lox duplications and deletions and e) crosses between a and b-d. Because a number of such genetically manipulated mice will be created (an estimated six per year) and because those generating the mice are in most case not trained in behavioral analysis, a core facility is necessary to screen all mutants for neural and behavioral phenotype. The effort applied to generating mutant mice will be wasted unless useful phenotypes can be detected by systematic analysis. A two-fold strategy will be used for this core. First, all animals will be tested on a fixed screening battery. The goal of the battery is to be sensitive to a wide range of behavioral effects, particularly those predicted in a mouse model of DS, and is based on validated screening batteries. Second, in cases where prediction is possible, tests will be designed to tap into the behavioral domains that are expected to be affected. Mice with productive phenotypes will be further pursued as the neurobiological and behavioral level in the individual projects or will be made available to other investigators. The basic battery will assess reflexes, screen for abnormal behaviors, assess sensory and motor function, emotionality, activity, habituation, pain sensitivity and hippocampally-dependent learning. Quality control procedures will be implemented to ensure reliability and consistency in behavioral testing, and the genetic and environmental backgrounds of the mutants will be carefully controlled to provide valid conclusions to be drawn from the data generated by this core. Additional services include the development and maintenance of a database of normative behavior data on the background strains used, and histology on all new mice by Dr. Rod Bronson. The core will be staffed by Dr. Linda Crnic, who has over 20 years experience assessing rodent models of mental retardation, and a full-time technician.
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