International Mammalian Genome Society

H12 Mutagenesis Screen for Behavioral Mutations in Mice

Lisa M. Tarantino¹, Gillian Leach¹, John Schimenti², and Maja Bucan¹. ¹University of Pennsylvania, Philadelphia, PA; ²The Jackson Laboratory, Bar Harbor, Maine

Random mutagenesis has been used primarily in the identification of single-gene traits that cause visible and developmental mutations. Our approach to mutagenesis involves a) identification of behavioral traits that can be modeled in rodents; b) identification of mouse mutants with anomalies in these simple behavioral traits; c) positional cloning of the genes that underlie these traits; and d) investigation of their relevance to the same or similar traits in humans. Our screen for single-gene behavioral mutations in mice involves phenotypic analysis of progeny of chemically (ENU) mutagenized mice using a set of assays for anxiety-related behavior (zero maze), neuromuscular function (rotarod), sensorimotor gating (analysis of the acoustic startle response), and rest/activity patterns (wheel-running activity).

As a first step towards the identification of behavioral assays appropriate for mutagenesis screens, we have collected baseline data on several inbred strains of mice for the measures listed above. These data confirm the genetic influences underlying these behaviors.

A screen of 500 F1 animals and progeny testing has identified several mutations. For example, we have identified one zero maze mutant, one prepulse inhibition mutant and one mutation that results in a short activity phase (alpha) of the circadian cycle. Initial phenotypic characterization of these mutations will be presented.