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

Abstract

Selection for increased and for decreased expression of the sex-linked gene brindled (Mo br ) in heterozygous females produced two lines with non-random X chromosome inactivation. In the High line the X chromosome 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 unmarked X chromosome 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-linked Pgk-1 locus proved that the percentage of brindled in the coat provided an accurate measure of the X-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 the Xce locus 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 the Xce locus.

Parental influences on X chromosome expression

“…X M and X p may have an equal probability of becoming inactivated (Johnston & Cattanach, 1981) or in some circumstances X p may be preferentially expressed (Falconer et al 1982). Using PGK-1 alloenzyme expression in erythrocytes, we have found parental effects on X chromosome expression using one allelic combination of Xce genes but no such effects with another.…”

“…Some studies indicate a 'paternal' effect i.e. X p has a higher probability of remaining active than X M (Falconer, Isaacson & Gauld, 1982), while others show no significant reciprocal cross differences (Johnston & Cattanach, 1981). In selection experiments with the X-linked gene brindled (Mo br ) (Falconer et al 1982) and viable brindled (Mo vbr ) (Cattanach & Papworth, 1981), a positive correlation was observed between the expression of brindled in mothers and daughters.…”

Further evidence for the importance of parental source of the Xce allele in X chromosome inactivation

“…X p having a higher probability of remaining active (Cattanach, 1975;Falconer et al 1982). In selection experiments with the X-linked brindled alleles Falconer et al (1982) and Cattanach & Papworth (1981) found a positive correlation between the expression of brindled in mothers and daughters. However, this 'maternal' effect was attributed to a physiological difference rather than the parental origin of the chromosome.…”

“…Some authors have found no reciprocal cross differences (Johnston & Cattanach, 1981) while others demonstrate a 'paternal' effect, i.e. X p having a higher probability of remaining active (Cattanach, 1975;Falconer et al 1982). In selection experiments with the X-linked brindled alleles Falconer et al (1982) and Cattanach & Papworth (1981) found a positive correlation between the expression of brindled in mothers and daughters.…”

Genomic Imprinting Leads to Less Selectively Maintained Polymorphism on X Chromosomes

“…In addition to the well-known examples of paternal-X inactivation in extraembryonic membranes of some eutherian females, including mice, rats, and cattle (Takagi and Sasaki 1975;Wake et al 1976;West et al 1977;Harper et al 1982;Xue et al 2002;Wagschal and Feil 2006), in preimplantation rodent embryos (Latham 2005) and somatic tissues of kangaroos and other marsupials (Sharman 1971;Graves 1996, Johnston et al 2002, there is also evidence of such phenomena in the somatic tissues of eutherian mammals. Preferential inactivation of the maternally derived X chromosome (rather than the usual pattern of random inactivation; Graves 1996) has been observed in the somatic cells of female mice (Cattanach and Perez 1970;Falconer and Isaacson 1972;Falconer et al 1982). More circumstantially, Hunt (1991) demonstrated that the viability of female mice with only one X chromosome was lower in mice whose X chromosome was paternally derived, suggesting that a number of genes relating to fitness may be expressed exclusively from the maternally inherited X chromosome.…”