Great mambo mouse brains created from human DNA

It often seems neuroscientists will go to the ends of the Earth to try to show that single genes control everything from the size of a particular brain lobe, to memory, speech or even intelligence itself. One of their favorite pet techniques is to take our genes, or even whole cells, and stick them into mouse brains to see what they do. As it happens, this method was recently used to great effect for an unassuming gene known simply as HARE5. Researchers from Duke found that if they gave some mice our human version of HARE5, and other mice the chimp version, the humanized mice grew great mambo brains.

Although it might seem that rabbits would be a good model organism to study a gene like HARE5, souping up mouse brains has a much longer tradition. We previously described attempts to make mice smarter by adding human microglial cells, and also to give them a deeply fissured human-style cortex by adding a gene known as TRNP1. We drew the line at covering efforts to make talking mice, but perhaps it is worthwhile now to mention that other researchers have in fact given mice our FoxP2 gene — a gene said to control our language skills — and made painful efforts to claim it actually enhanced mouse learning and affected synaptic processing.

HARE5 itself stands for human accelerated regulator enhancer of FZD8, but this FZD8 is another whole story. I know we are throwing out a bunch of genes here, but there is a method to the madness. Strange as they may at first seem, the odd letters in genes names are often just a practical description of what the poor mouse (or sometimes a fly) looks like after that gene is artificially crippled in its genome or proteome. For example, in the the case of mutated FZD, or “frizzled” and also its partner “disheveled,” the hairs and bristles of a fly grow in every direction.

The human version of HARE5 differs from that of the chimp at exactly 16 base pair locations. That difference apparently causes cells in the cortex to increase their rate of proliferation early on in development, although others effects could be at play. In mice, this change resulted in a 12% increase in the overall size of the cortex. We already mentioned above that the TRNP gene helps make a thick luxuriant human cortex. Both HARE5 and TRNP are genes that are involved in what can generally be called the cell cycle. In other words, they effect how fast cells churn through periods of division, and periods of ordinary work. In addition to controlling the rate of cell division, these genes also control how many times a cell lineage will continue to divide, and also when, where, and in what direction subsequent cell progeny migrate and ultimately put down roots.

Whether or not these super mice really have clear benefit from the extra neural tissue remains to be seen. That is not really the point of this. For us, these kinds of studies may, or may not be a big step forward to intelligently augmenting our own brains. The hope is we will eventually be able to hard code some kind of developmental genetic plan for building the kinds of brains we ultimately want or need. The larger guiding question though, and one to which we will return here, is not so much what kind of brain do we actually want, but what do we want it to be able to do?