Erin Stenson

Mus Musculus was randomly mutagenized using N-ethyl-N-nitrosourea (ENU). Mutations on Chromosome 5 were selected using the Rw inversion, a visibly marked, recessive, lethal inversion that covers almost fifty megabases (Mb). Multiple mutations were isolated from the subsequent three-generation mutagenesis screen, one of which was lethal 6. Using a combination of complementation tests and recombinational mapping, the lethal 6 region was narrowed down to less than 1.4 (Mb). There were thirty-eight candidate genes in this region of which 4 had already been mutated and yielded viable progeny. The coding regions of 80% of the remaining thirty-four genes have been ruled out from being lethal 6, although it is still possible that ENU affected the regulation of one of these genes. Mice homozygous for lethal 6 die around E8.0 and preliminary results from blastocyst outgrowth assays suggest that they are unable to implant. Introduction: The process of early mammalian development is remarkably similar between different species. Embryogenesis follows the same patterns, and the basic processes are controlled by the same conserved genes in different organisms. To discover the genes necessary for normal human development, the organism Mus musculus is a good model because approximately 93% of mouse loci are found in the same position in both mice and humans (Mouse Genome Sequencing Consortium, 2002). Mus musculus is also a good model organism because they have a short gestation period, big litter sizes, and short life cycles. Genes that are necessary for embryonic development of Mus musculus will most likely be necessary for the embryonic development of humans. The genes required for embryonic development of Mus musculus should have very similar sequences and