> I was looking into it further…this is one example I found (of many) of actual geneticists expressing it the same way as these folks. It seems like a pretty standard way to write it.

Depends on what you mean by standard, I guess. However, in either case it is incorrect, and I gave you an article literally published by Jax, which is the ultimate authority on both these animals and their nomenclature, saying as much.

It’s pretty standard for academics and practitioners to refer to lactate as “lactic acid”, and to think of it as a waste product, and yet both of these notions are totally incorrect.

> Especially when a cursory search of Jackson’s catalog seems to indicate that their Ifngr1-/- mice are all C57BL/6J.

You’re a little confused on the terminology here, which is understandable because these databases assume proficiency in it. Ifngr1 is a gene, not a strain (interferon gamma receptor 1). The “-/-“ refers to a double-knockout. Jax produces 6J-background mice with a huge number of knockouts/knockins/mutations, they supply over 8,000 strains and most are built on 6J. If you search the database for the string “ifngr1” you will see many substrains with that string in their denotation. The correct notation for ifngr1 double knockouts is probably B6.129S7-Ifngr^(1tm1Agt)/J, where “J” refers to the colony maintainer (in this case, Jackson Laboratories), the post-hyphen string refers to the gene of interest, and “tm” denotes the targeted mutation of that gene. B6.129S is a 129 substrain commonly used when producing congenic strains.

But, again, I don’t actually know if that’s the correct strain because they didn’t actually give the right notation.

> To me, questions of whether these were the best test subjects seem more pertinent than potential ambiguity in terminology

They’re the same question, and that’s my point. People don’t get that the ambiguity impairs our ability to correctly evaluate the comparisons being made between these subjects. A mouse denoted as “C57BL/6” in your study could literally be one of several thousand strains, with tens of thousands of known and documented mutations which may of may not be present in your cohort, which is to say nothing of the undocumented influence of drift.

As to whether they’re the best subjects, the unfortunate fact is that we don’t really have an alternative genetic background anywhere near as standardized as these animals. The problem is that nutrition has a habit of trying to shift the reference frame to make low quality data and inferences look high-quality simply because it’s the best they have. See the GRADE scandal for a key example of this.

> Is there more reason to suggest they should have specified?

Geneticists understand that using rodents as a test subject not only means you need to take a huge grain of salt when comparing macroscopic results to humans, but that we also need a big grain of salt when comparing mice cohorts to other mice cohorts, at least when they are of different genotypes.

It just depends on how confident you are that all accumulated drift and mutations in all existing laboratory mice of each denoted strain have have zero effect on the physiology of the animals. Personally, my confidence in this is zero.

If you want, I can give you recent literature on this issue of growing, undocumented genetic diversity in common lab strains and why it’s a problem.

There is an unfortunate general ignorance outside of genetics of what these mice really are and how to think about them. Institutions that have their own colonies with have qualified and knowledgeable people as maintainers, but they aren’t writing the papers. In a nutshell, they are the renewable testing grounds of a genome we know and control, making them a valid background for a) interventions in that genome and b) interventions among genetically identical cohorts.

Black-6 descendant strains (like B6J, which this study likely used) are not intended to ask questions of diet or drug effect and extrapolate across non-identical colonies or other species, but rather to have a controlled genetic background against which to test the effect of interventions and/or genes which we add or subtract, ie knockouts.

The way that Jackson maintains B6J is by periodically reintroducing frozen gametes from the original “Adam and Eve” B6J pair, and using them to refresh the source colony based on the reference genome, which for B6J is called GRCm38.p6.

However, the inevitable fact is that as soon as you take mice away from that colony and start breeding them, they immediately start diverging from the source genome, accumulating mutations which have the potential to alter their physiology and bias study results. This is why it’s so critically important that you always denote the exact substrain being used, but also more broadly that we take a huge grain of salt when we see some change in outcomes in a mouse population for which we don’t really have an precise background rate of that outcome. It’s not exactly the cohort that’s the problem, since if you’re using two groups of mice that are presumably nearly genetically identical to each other the deviation is null, but rather the comparison between studies.

eg, study 1 used “Black-6” mice and found diet A had 1.5 OR for some outcome compared to diet B, study 2 used “Black-6” mice and found diet A had 0.9 OR for the same outcome compared to diet B, but if we have no idea what the actual genetic differences between those two colonies were, the comparison is kinda fucked. We don’t know their distance from the reference genome, if the distance from each is symmetrical, if both have had cryorecovery done and at what points, etc. These mice are under intense selection pressure to breed large litters and survive a very unnatural laboratory environment, and we know there are substantial genetic differences accumulating among them, both from those environmental stimuli and from drift. And then you start bundling these things into meta-analysis and you have this growing source of invisible confounding.