Strained relations

26th February
By Jacqui White

One significant difference between the strains is the deletion of the Crb1 gene  in C57BL/6N mice, which can lead to progressive sight loss. doi:10.1186/gb-2013-14-7-r82

One significant difference between the strains is the deletion of the Crb1 gene in C57BL/6N mice, which can lead to progressive sight loss. doi:10.1186/gb-2013-14-7-r82

C57BL/6J, the strain of mice that gave us the first mouse reference genome, and C57BL/6N, the strain of mice that is being characterised in an international effort to discover each gene’s function, came from the same family but are separated by 63 years and over 220 generations. It’s crucial that researchers using data sets from these strains are aware of the differences that have developed during their decades apart.

Surprisingly, a recent study, in which the Mouse Genetics Project at the Wellcome Trust Sanger Institute participated, has revealed only 279 validated differences between the genomes, of which only 51 affected the coding sequence of genes directly. Furthermore, between the four different research centres across Europe working on this study, only 27 characteristics were found to be consistently and significantly different.

While these differences, including fat mass, blood glucose levels and heart rate, are relatively few in number, individually they could have a big impact on a piece of research. After all, when it comes to genetics, the devil’s in the detail.

One example is a single base pair deletion in a gene called Crb1; this deletion, found in C57BL/6N mice, but not C57BL/6J mice, means that C57BL/6N mice do not make the Crb1 protein involved in maintaining the shape of photoreceptors in the eye. In the absence of this protein, photoreceptors degenerate and regions of decreased pigmentation appear on the mouse retina, resulting in progressive loss of sight. This gene performs the same function in the human eye, so any researcher using a C57BL/6N mouse as a model must be aware of this degeneration and adjust methods accordingly.

Much research in the past has been performed on the C57BL/6J inbred strain of mice. It was the original mouse reference genome for the whole genome sequencing effort and it is the strain that many genetically modified mouse lines were bred onto to study defined alterations in the mouse genome. Meanwhile, the large international effort to knockout every protein coding gene in the mouse one at a time, which will assess the consequences of turning off each gene, uses mice with a C57BL/6N genetic background. This will increase the profile of the C57BL/6N inbred strain, with far more research labs around the world using it as a model.

This study of just 400 distinct characteristics only touches the surface of what may be different between these inbred strains. However, even with this limited number of characteristics, it has identified some differences that should be considered carefully.

More generally, researchers must be mindful that C57BL/6N and C57BL/6J, though still closely related after all these years, are phenotypically distinct strains of mice. As such, they should be sure that they thoroughly understand the normal characteristics of their chosen inbred line before making conclusions about abnormalities that they observe.

Jacqui White is a principal scientific manager and leader of the Mouse Genetics Project Phenotyping Team at the Wellcome Trust Sanger Institute.

References