Behavior and mutagenesis screens: the importance of baseline analysis of inbred strains

Random mutagenesis as a means of identifying the function of genes has been used extensively in a variety of model organisms. Until recently it has be en used primarily in the identification of single-gene traits that cause vi sible and developmental mutations. However, this genetic approach also has the power to identify genes that control complex biological systems such as behavior. Mutagenesis screens for behavioral mutations require careful con sideration of many factors, including choice of both assays and background strains for use in mutagenesis and subsequent mapping of the affected gene or genes. This paper describes behavioral assays for monitoring motor coord ination on the accelerating rotarod, anxiety-related behaviors in the eleva ted zero maze and sensorimotor reactivity, gating, and habituation of acous tic startle. These five physiological or neurological behaviors can represe nt potential endophenotypes for a variety of neurological and psychiatric d isorders. The significant degree of strain- and sex-specific differences in the performance of four inbred strains of mice (C57BL/6J, C3HeB/FeJ, DBA/2 J, and 129/SvlmJ) in these behavioral assays illustrates the importance of performing baseline analysis prior to behavioral mutagenesis screens and ge netic mapping of selected mutations.