Ethylnitrosourea mutagenesis and the isolation of mutant alleles for specific genes located in the T region of mouse chromosome 17.

Ethylnitrosourea mutagenesis of spermatogonia in male mice is very efficient and makes it practical to isolate new desired mutant alleles by subsequent progeny screening. This is demonstrated for three genes in the t region of chromosome 17. The first, a mutation designated t-int, interacts with the dominant mutation, T (Brachyury), to produce a tailless mouse. Previously, mutant alleles of the t-int gene were available only in t haplotypes, where they are part of a t chromatin block within which recombination with wild-type chromosomes is inhibited. In addition to t-int, new mutations at the quaking and tufted loci were obtained, as well as at several loci not on chromosome 17, e.g., an X-linked lethal that causes a mottled phenotype in the heterozygote and four new mutant W alleles on chromosome 5. In the experiment, an average of one fertilizing spermatozoan in 1500 was mutant at a given locus and an average of one male in five was able to sire mutants at that locus.