Comment by robwwilliams

I have read it now. Comment below. As to an increase in mouse neocortical volume—they have ZERO data. Look at their figures 1g and 1h and weep for the crap reviewing.

Personal dissections about 2-3K (lifetime). Total over 35 years of the lab: about 20,000.

Just reviewed the paper. Extremely elegant flamingo dance. But let me reserve my comments to the Hacker News theme of an enlarged brain (or really an enlarged neocortex). The key panels on this topic are Fig. 1g and 1h. OMG, the dissections of these "best examples" are sad–– the olfactory bulbs are serious torn and paraflocculi are detached. The histogram that is Fig 1h has a grand total of 6 measurement for the human transgenic mouse line and 4 (four) points for the control. Hey when you have a statistically significant result why mess it up by evaluating 10 of each of the two groups. You might not get published in Nature or airplay on HN, and would that not be a shame?

As for the measurement of brain size, it is a planimetric projection of the area of the dorsal surface of the neocortex. This is a lame way to do morphometry. Squish the brain a bit and the area will expand beautifully—and by way more than 6.5%.

One last comment on the genetics of these animals. The are probably incorrectly stated to be at least F8 progeny of the mixed 129-B6N embryonic stem cells. I hope they mean N8 backcross progeny––that is to say, 8th generation congenic lines. But in this case they appear to have backcrossed weirdly to a different type of B6; the standard C57BL/6J strain. All of this means that even in the best case, they have three different genomes banging around in supposedly co-isogenic cases and their controls: 1. chunks of 129 strain chromosomes that will still be common even at 8 generations, 2. chunks of B6N chromosomes that will also be common at 8 generations, and of course the B6J background strain. You would have to carry out sparse whole genome sequencing or use the GigaMUGA array to unconfound the genetics in this study.

For the claim of increased neocortical size—-the topic of this HN thread, they show 4 controls versus 6 transgenic mice. Not sure if they did this blinded. Would depend mainly on when they did the genotyping.

Highly linear in vivo and close to 1. Brain has a lot of fat but not a big deal in mice. Only fine point is that the density of brain varies depending on fixation protocol but almost always by less than 5% if you get the osmolarity of the solution just right.