As these GEITP pages have described several times before, “purely inbred mouse lines,” as well as established cell culture lines, are almost always subject to change, and scientific researchers need to be aware of, and on the lookout for, such alterations. This is simply “biological variation” that we now know reflects normal “genetic drift” as well as epigenetic effects –– that occur as a function of time. In the late 1970s, I recall picking up a delivery box from the loading dock at NIH in the late afternoon sunshine, and seeing the coat color of “C57BL/6J mice” being a lighter brown (rather than the true black or very dark brown, as expected). Also, many of us have experienced experimental results in one or another cell culture line that differed from what had been seen previously.
The C57BL/6 strain originated at The Jackson Laboratory (Bar Harbor, Maine) in the 1920s, but the inbred line has been derived and re-derived several times since –– due to serious health issues in the mouse colony as well as devastating fires that destroyed many of the mouse facilities. However, “C57BL/6J” has become “the standard” as a “genetic background” for many hundreds of transgenic mouse lines, and its draft genome seuence (in 2oo2) was the first Mouse Genome to have been ‘completely’ sequenced. (About 268 genes are completely different between mouse and human; the remaining >20,000 genes have orthologs in both species.)
The attached brief article describes the pair of C57BL/6J mice that were selected and bred in 2005, and their progeny (numbering in the hundreds of thousands) have spread around the world. To keep the mice as genetically similar as possible, researchers have repeatedly bred brothers with sisters; this brother-sister inbreeding is something quite remarkable that can be done more successfully in mice than in humans as well as even rats — without having serious and undesirable genetic diseases. The genome of the C57BL/6 mice that the JAX lab sells today has thousands of genetic differences from the mouse reference genome, which was created in 2002 from three mice from the substrain C57BL/6J.
Other suppliers have inadvertently created divergent substrains of C57BL/6 mice when they’ve bought rodents from JAX and bred them over several generations. For example, in 2016, the company Envigo in Somerset, New Jersey found that C57BL/6 mice at six of its 19 breeding facilities around the world had acquired a mutation in a gene related to the immune system. The company notified the researchers who had bought these mice, and asked customers to specify which location they preferred to source mice from in the future, given that the company’s stocks were no longer identical.
Nature 16 Nov 2o17; 551: 281