Induction of new mutations in a mouse t-haplotype using ethylnitrosourea mutagenesis

N-ethyl-N-nitrosourea (ENU) was used to induce mutations within the tw5-haplotype of the mouse to make possible a further study of gene arrangement in t-mutants and to provide potential landmarks for cloning and sequence studies in the region. Two independent mutants were isolated for each of three loci in the t-region, brachyury (T), quaking (qk), and tufted (tf). The new Tkt alleles produce tailless mice when a tct mutation is present in trans. The new qkkt alleles are recessive and homozygous lethal. They are viable, male fertile, and cause seizures and quaking when paired with the qk mutation which previously defined the locus. The tfkt mutations are recessive and phenotypically similar to the mutant alleles available in non-t chromosomes. The mutations were induced in the tw5-haplotype at an average per locus frequency of 1 in 1500. Their isolation demonstrates the power of this technique for obtaining the specific mouse mutants that are needed to genetically dissect a complex mammalian system.