International Mammalian Genome Society

H11 Mouse Mutants from Chemical Mutagenesis of ES Cells

Robert J. Munroe¹, Rebecca A. Bergstrom¹, Qing Yin Zheng¹, Richard Smith^1,3, Simon W. John^1,3, Wayne F. Frankel¹, Kerry J. Schimenti¹, Lisa Tarantino², Maja Bucan², Victoria L. Browning¹ and John C. Schimenti¹. ¹The Jackson Laboratory, Bar Harbor, Maine 04609, USA; ²Univ. of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6140

The drive to characterize human gene functions on a global scale has spurred interest in generation of mouse mutants by phenotype-driven mutagenesis. To overcome drawbacks associated with classical whole animal chemical mutagenesis, we devised protocols to generate germline chimeric mice from embryonic stem (ES) cells mutagenized with ethylmethanesulfonate (EMS). These chimeras transmitted mutations affecting several processes, including limb development, hair growth, seizure susceptibility, behaviour, and gametogenesis. This technology affords certain advantages over traditional mutagenesis, including the abilities to: 1) easily monitor and control mutation rate, 2) conduct shortened breeding schemes, and 3) perform screens for mutant phenotypes directly in ES cells before generating mice.