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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    Injection chimaeras 33 respectively. Thus it seems that cells are most unlikely to participate in the development of an embryo if they deviate from it in age by more than 2 days. Ingenious use was made of the possibility of injecting single cells into blasto¬ cysts, to investigate the time of X chromosome inactivation (see Chapter 9) in mice (Gardner & Lyon, 1971). The blastocysts which provided donor cells were from albino females mated to males carrying Cattanach's translo¬ cation: female progeny from such a mating would have coats mosaic for albino and agouti, corresponding to the inactivation of the translocated and normal X chromosomes respectively. The recipient blastocysts were from matings which would yield sandy-coloured progeny. Thus if any chimaeras were produced with both albino and agouti, as well as sandy, patches in the coat, it would indicate that the single injected cell was genetically female, and had not yet undergone X chromosome inactivation, so that its cell progeny included some with the translocated X and some with the normal X inactivated. Chimaeras with albino but not agouti, or agouti but not albino, patches would indicate either that X inactivation had already occurred by the time of injection; or that by chance cells of one donor type only had been selected in the ancestry of the melanocyte population; or, in the case of albino patches only, that the injected cell was genetically male (Fig. 14). When donor cells were taken from blastocysts 3} days p.c., nine of thirty- two young that survived to weaning showed chimaerism, with hairs of donor colour distributed widely throughout the coat despite the origin of their melanocytes from a single injected cell. Five of the nine chimaeras showed agouti patches, indicating that the injected cell had been female. Since four showed white patches also, it seems clear that X-inactivation, defined as an irreversible loss of gene function, has not taken place by 3^ days p.c. A similar result was obtained using 4^-day donor blastocysts (Gardner, 1974). One conclusion of general validity for early development can be derived from all the studies that have been carried out on both injection and aggrega¬ tion chimaeras. No instance has been found of a tissue or organ, however small, which in a chimaeric animal is always formed of one component only. This implies that it is groups of cells, rather than single cells, which are directed towards particular developmental pathways and thus give rise to particular tissues and organs. The consequences of this type of analysis will be explored in more detail in Chapter 10.