ABSTRACT

This chapter explores current and potential applications of random chemical mutagenesis to identify novel rest: activity mutations in the mouse. It describes the mutagenesis procedures and behavioral assays and constraints of genetic analysis in the study of rodent behavior. The procedure for chemical mutagenesis involves administration of the mutagen N- ethyl-N-nitrosourea (ENU) to 7 to 10-week-old mice with three weekly doses of 100 mg/kg by intraperitoneal injections. Since ENU is mutagenic for mouse spermatogonial stem cells, successfully mutagenized animals will be rendered temporarily sterile. A Macintosh-based interactive program, Cireadia, is used to rapidly visualize, analyze, and quantitate the rhythmicity and activity of mutant mice. Circadian rhythms can be characterized by three quantitative parameters: period, phase, and amplitude. To identify potential mutants, wheel-running activity of progeny of ENU-treated mice is examined in light-dark and constant dark conditions. Almost all Gl progeny exhibit robust activity, typical of most inbred mouse strains.