Mammalian chimaeras / Anne McLaren.

  • McLaren, Anne.
Date:
[1976]
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Mammalian chimaeras / Anne McLaren. Source: Wellcome Collection.

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    102 Chimaeras versus mosaics demonstrated directly, though organ-specific differential adhesion of dis¬ aggregated cells in culture is well established. The results from chimaearas of one strain combination, (C57BL x C3H)Fi<^'multiple recessive, suggest that some genotype-specific cell adhesion may be occurring (see Chapter 10). In contrast, a series of chimaeras between congenie strains (CBA-T6^CBA-p; Mystkowska & Tarkowski, 1968), in which the components are very close to one another genetically, closer than in most X-inactivation mosaics, showed evidence of a rather small patch size, both in the coat and in the spermatogenic tubules (see Chapter 4). The time of origin of heterogeneity could also aifect both patch size and the variation in proportions of the two components. If development encom¬ passes a succession of sampling events (Chapter 10), the earlier in this succes¬ sion the heterogeneity arises, the greater will be the variation among animals and among organs. In particular, the derivation of the foetus from a rela¬ tively small number of cells in the inner cell mass of the blastocyst must be responsible for much of the variation seen among chimaeras. X-chromosome inactivation has not occurred at this stage of development, so this cause of variation will be absent in X-inactivation mosaics. As for patch size, it is clear that in a situation of largely clonal development with restricted cell mingling, the later heterogeneity arises, the smaller will be the final patch size. This argument has been used by Deol & Whitten {\911a, b) and by McLaren et al. (1973) to suggest that X-inactivation in some tissues may not take place until a relatively late stage of development. Nesbitt (1974) has claimed that the larger patch size reported by Deol & Whitten (1972a) in the pigmented retinas of chimaeras than of X-inactivation mosaics would be consistent with X-inactivation occurring at about the time of implantation. She argues that provided cell mingling occurs to the same extent in both groups and is restricted, so that the distribution of the two cell populations never becomes random, and provided that the disruptive effect of cell migration on clone size is independent of initial clone size, the ratio of the mean patch sizes in the adult retinas should remain unchanged from the time of X-inactivation to the adult. (In fact Lewis (1973) has shown that the effect of cell migration is not independent of initial clone size, but disrupts small clones to a greater extent than large clones. This will tend to increase the patch size ratio of chimaeras relative to mosaics as development proceeds.) Since in the adults examined by Deol «& Whitten (1972^), the mean patch size in the pigmented retinas was ninefold greater in chimaeras than in mosaics, Nesbitt infers that at the time of X-inactivation the chimaeric patches, and hence also clones, would have been not more than nine times greater than those in mosaics, i.e. each chimaera clone should have contained no more than nine cells. It is known that X-inactivation does not take place before the blastocyst stage (Gardner «fe Lyon, 1971). A chimaeric embryo, at least up to the blastocyst stage, is in fact made up of only two patches, one