Sex-linked variegation modified by selection in brindled mice

Abstract

SUMMARY: The sex-linked gene,brindled, in the mouse produces a coat-colour variegation in heterozygous females. There is much individual variation in the relative areas of mutant and wild-type colour, but it was not known if any of this variation was genetic. The main object, when the experiments were started, was to test the simple expectation of the Lyon hypothesis, that ifX-inactivation is random the variegation should not be modifiable by selection. On the assumption that the variegation is due toX-chromosome inactivation, modification by selection would show that the inactivation process, or some property of the derived cell populations, is under genetic control. Heterozygous females were accordingly selected for the area of coat showing the mutant colour. Selection based on individual phenotypes was ineffective, but four cycles of reciprocal recurrent selection based on progeny-means produced a ‘High’ line with 64% mutant area and a ‘Low’ line with 30% mutant area, from a base population with 53% mutant area. Autosomal modifiers were not responsible for the response; the difference between the selected lines was entirely due to properties of theXchromosomes carrying thebrindledgene. The changed properties of theXchromosomes were not restricted to the locus ofbrindled, but extended at least as far as the locus oftabby. The chromosomes carrying the wild-type allele ofbrindledwere not altered by the selection, but normalXchromosomes from other strains affected the degree of variegation. It was concluded that the difference between the selected lines was due either to non-random inactivation or to somatic cell selection. It was not possible to distinguish between these two mechanisms. The results obtained in these experiments with a structurally normalXchromosome were in all essentials similar to those obtained by Cattanach with hisX-autosome translocation.