Non-random X-chromosome inactivation in the mouse: difference of reaction to imprinting

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Abstract
Summary: Selection for increased and for decreased expression of the sex-linked gene brindled (Mobr) in heterozygous females produced two lines with non-randomXchromosome inactivation. In the High line theXchromosome marked by brindled was active in about 60% of cells, while in the Low line it was active in about 25% of cells. The whole of the difference was caused by the chromosomes carrying brindled: neither the unmarkedXchromosome nor the autosomes were differentiated. There was a positive correlation between the expression of brindled in daughters and mothers. This was probably not caused by residual genetic variation, but was more probably a maternal effect similar to that described by Cattanach & Papworth (1981). On this assumption the daughters' scores were adjusted to a standard maternal score. Enzyme assays on females doubly heterozygous for brindled and for the sex-linkedPgk-1locus proved that the percentage of brindled in the coat provided an accurate measure of theX-inactivation proportions in the blood, liver and kidney. The accuracy was improved by adjustment for maternal score. In the selection lines, brindled was always inherited from the mother. When brindled was transmitted by male parents the probability of activation of its chromosome was increased by 8 percentage points in the High line and 18 in the Low line. This effect of the parental source is much greater than has previously been reported. The responses to selection can be interpreted in terms of theXcelocus controlling the activation probability, different alleles on the chromosomes carrying brindled being selected in the two lines. If this interpretation is correct, the alleles on one or both of the chromosomes carrying brindled were different from any of the three known alleles. The different effects of male transmission in the two lines can be described as a difference between the two chromosomes in their reactions to imprinting. This difference might possibly also be due to theXcelocus.