DYSTROPHIN EXPRESSION IN HETEROZYGOUS MDX + MICE INDICATES IMPRINTINGOF X-CHROMOSOME INACTIVATION BY PARENT-OF-ORIGIN-DEPENDENT, TISSUE-DEPENDENT, STRAIN-DEPENDENT AND POSITION-DEPENDENT FACTORS/

Inactivation of one X chromosome (X inactivation) in female mammals re sults in dosage compensation of X-chromosomally encoded genes between sexes. In the embryo proper of most mammals X inactivation is thought to occur at random with respect to the parental origin of the X chromo some. We determined on the cellular level the expression of the X-chro mosomally encoded protein dystrophin in skeletal and cardiac muscle of female mice heterozygous for a null mutation of the dystrophin gene ( mdx/+). In all muscles investigated (cardiac, anterior venter of digas tric muscle, biceps brachii and tibialis anterior muscle) we found a m osaic expression of dystrophin-expressing versus non-expressing cells and determined their proportion with respect to the parental origin of the X chromosome. In all groups of mdx/+ mice the level and pattern o f dystrophin expression were found to be dependent on the parental ori gin of the mdx mutation. Additionally, the extent of dystrophin expres sion was clearly dependent on the mouse strains (C57BL/10 and BALB/c) used to produce heterozygous mdx/+ mice. Variable differences and patt erns of dystrophin expression in skeletal versus cardiac muscle were f ound that were strictly dependent on the parental source of the mdx mu tation and the strain used to breed mdx/+ mice. Moreover, dystrophin e xpression was found to be different between the right side and the lef t side of the body in individual muscles, and this difference was clea rly dependent on the parental origin of the X chromosome. Our data pro vide evidence that in the mouse embryo proper there is a non-random di stribution of cells showing inactivation of the paternal versus the ma ternal X chromosome in skeletal and cardiac muscle, indicating a non-r andom X-inactivation. Besides gametic imprinting, strain-, tissue and position-dependent factors also appear to bias X inactivation.