Remarking on the Unremarkable: Co-colour chimeric mice

In developmental biology and stem cell science, the use of mice, and the creation of different kinds of chimeric mice have become both methods for validating and testing research questions, as well as a means for conducting translational research. Co-colour mice, a version of intraspecies chimera, while visually remarkable, are often overlooked in media and ethical debates on the creation of chimeric organisms. Yet, co-colour mice provide an avenue for thinking about chimeric organisms as important methods and how different research subjects and techniques are connected and regulated.

Chimera mouse produced offspring. NIH. Source

Co-colour mice are visually striking: usually, cells from a white or brown mouse are injected into a mouse blastocyst of a different colour, resulting in a striped mouse of white and brown. Co-colour mice are diploid, meaning that they contain a 50/50 contribution of cells from donor injected cells, and the host blastocyst: by inserting donor cells into a host embryo, in equal amounts, there is a 50-50 genetic contribution to the development of the organism. The experiment offers a clear, visual validation of successful chimerism and when the co-colour mice are bred, the resulting pups (and their colouring) offer further confirmation of effective cellular mingling, that can be passed on generationally.

Such mice have been made since the 1960s and continue to be used to validate cell integration and cell fates. For stem cell and developmental biologists, making co-colour mice offer a standard, trusted method for understanding lineage and fate mapping of cells. Because co-colour mice are a version of intra-species chimera; and because of their status as animals, they are not subject to many legal restrictions. In particular, their production is not subject to gamete contribution restrictions, as well as restrictions related to the amounts of cellular mixing. These two factors are what make co-colour chimera useful as validation tools for how cells integrate and function.

Speaking with scientists in our study who work with intraspecies chimeric mice, to test embryo development, cell potency, and fate mapping, many referred to these mice as a critical research method and a standard tool for validating their work. They spoke of the mice as useful tools and methods, which have been used for decades, and continue to be produced. For many developmental biologists there is a ‘taken for grantedness’ to making chimeric animals in this context.

Chimeric mice generated using B6 ES cells and B6 Albino A++ blastocysts. The contribution from the ES cells is higher in the mouse on the left, and the contribution from the blastocyst donor is higher in the mouse on the right as judged visually by coat colour. Source

Co-colour mice are respected as tools but have also become ‘invisible’ in some ways. This is because they have become a standard method for doing basic research and they have been used for over 50 years. What is remarkable about co-colour mice though, is not so much that they are made and how they look, but how unremarkable they have come to be seen as tools in a form of scientific research that is laden with ethical debates, due to the potential in ‘chimera biology’, for mixing human and animal material, and what that might mean for human-animal relational divides.

In regulation, the co-colour mouse is framed as an animal (and method) subject to protections under the Animals (Scientific Procedures) Act (1986) in the UK. As a kind of chimeric organisms, in biology, they have been used for over 50 years. This points to the remarkable ‘unremarkable-ness’ of a 50/50 contribution and technique in chimeric research. Combining human cells with animals is strictly regulated but co-colour mice are intraspecies and therefore, are not subject to restrictions relating to limiting high contributions of donor cells and forms of integration.

Gardner, R. 1968. Nature Vol. 220. Pp. 596-597.

Alternate registers of value are assigned to different species in chimeric research, and research that entails inter or intraspecies work. Indeed in the UK, a co-colour mouse offers an example of chimerism as an extraordinary research tool. Co-colour mice, offer a window for thinking about how different scientific methods are possible as well as how these mice are a foundation for building biological knowledge, but are also modulated, confined and shaped by regulation, ethics and law. As striking as co-colour mice appear, they have come in regulation and media controversies, to be invisible in some ways because they are chimeric organisms that do not cross species lines. As such, while regulators instantiate restrictions on specific species mixing, particularly human embryo and cell involvement, co-colour mice go largely unseen in public and media debates. Drawing attention to co-colour mice as a remarkable method in developmental biology offers a brief case to begin thinking about how value is assigned, how species hierarchies are enacted, who counts as research subjects or methods, and what constitutes different kinds of research subjects that matter, and get to be made.