Yes that paper is great. My comment was directed more at those criticizing mouse models than this particular paper. Techniques are lovely; results are hopeful.

Yes that paper is great. My comment was directed more at those criticizing mouse models than this particular paper. Techniques are lovely; results are hopeful. But I need to see this generalized before talk about translation in HN or elsewhere, or yet another discussion about lousy mouse models and the necessity of “in mice” in every title. From my point of view my comments were needfully and purposefully inflammatory to break the fever. Hard to believe, but scientists (myself included) can be exceedingly stubborn and resistant to necessary paradigm changes such as incorporating genetic diversity into studies. The principal reason mouse models are critiqued in HN and at NIH is that they are regarded as translationally ineffective. Many of my colleagues often say that mice are poor models of human diseases X, Y, and Z. To be blunt they usually do not really know what they are talking about. What they mean is that B6 is a bad model. But B6 is regarded as THE MOUSE. Is any one human a great model of human traits and diseases? Why do we allow this for experimental work. It truly is N=1. We also have a community-wide fixation on moving all mutations and transgenes on to the glorious or notorious C57BL/6 strain. Without background genetic variation we have fragile models that often do not generalize across strains of mice. “Our current models are mannequins we dress up with sparse data from a few experiments and send down a publication catwalk, praying they don't toddle and trip. What we need are powerful, diverse, and well dressed models that can navigate a landscape, not a catwalk. As a community we have not begun to grapple with this issue, but one certainty is that we will require extraordinarily well structured data sets for humans and for experimental models, to make accurate predictions.” from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751652/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751652/ As to your request that I review the Methods section more carefully — done. And I do not see any errors of commission on my part. All of the lines that you list above are C57BL/6J (B6) or congenic mice on a nearly pure B6 background. The first is the reference B6 inbred strain. #2 is a B6 congenic (B6.xxx) #3: The Pvalb mouse is at least a five-generation backcross to B6, and therefore also nearly congenic. This line is likely to have been backcrossed for more generations to B6 at JAX; to the point that it is likely to be >95% B6. #4: The nomenclature of this line clearly states that it is a B6 congenic. The typical minimum number of backcrosses to list as a cogenic is 10, but this is a popular line of mouse and may have been backcrossed for even higher purity. #5: Finally, the APOE4-5XFAD mice are 97% C57BL/6J. “…mice homozygous for APOE4, and hemizygous for the 5XFAD transgenes, on a background strain 97% C57Bl/6J and 3% SJL; mice were then inbred between 5xFAD+ and 5xFAD- resulting in littermates E4+/+:FAD+ and E4+/+:FAD−.”