Identification and Characterization of Lethal 6: a Chromosome 5 Embryonic Lethal Mutation in Mus musculus
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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.
dissertation or thesis