Size regulation does not cause the composition of mouse chimaeras to become unbalanced

Mouse chimaeras made by aggregating two 8-cell stage embryos undergo size regulation shortly after implantation. Thus chimaeric pups are approximately normal size at birth despite their origin from two complete embryos. Chimaeras of some strain combinations are genotypically unbalanced such that cells of one strain almost always predominate. For example, the BALB/c inbred strain often makes a low contribution to chimaeras. This genotypic imbalance in the composition could arise by selection against BALB/c cells. Selection may be particularly acute at the time of size regulation. To investigate if the mechanism(s) responsible for size regulation could cause the low contribution of BALB/c cells, we compared the composition of an unbalanced series of chimaeras, produced by aggregating two complete 8-cell stage embryos, with a similar series of chimaeras made by aggregating two half 8-cell stage embryos. In each case the unbalanced strain combination was BALB/c<-->[(C57BL x CBA/Ca)F1 x TGB] and parallel studies were undertaken with a genotypically balanced strain combination. For each chimaera, the composition of the fetus, placenta and extraembryonic membranes were determined at E12.5. When two half embryos were aggregated the BALB/c strain still made a poor contribution to all the tissues of the mid-gestation conceptus. This implies that this strain combination remained unbalanced even when size regulation was absent or minimal. Therefore, size regulation did not play a major role in reducing the contribution of BALB/c cells and producing the phenotypic imbalance in the chimaeras.