The hosts walk through experimental data showing that the yak version of the RETSAT gene, RETSAT Q247R, produces a larger spike in the compound ATDR compared to a control version of the gene, establishing a causal link between the mutation and higher ATDR levels. They reason that this gain-of-function effect may work like a threshold or tipping point, where ATDR needs to reach a certain concentration to signal oligodendrocyte precursor cells and stem cells to produce more myelin, and where falling below that level under hypoxia or in MS could impair repair.
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The discussion references three charts comparing control RETSAT to the RETSAT Q247R (yak) version, with the mutant version farthest to the right showing the largest ATDR spike.
446 words · auto-generated from the episode video
1:14:14gets processed in two major branches. One way is just the classical branch which is retinol into retinel into retinoic acid. Chemists are so annoying about this, right? It's it's like come on guys. Anyways, the other way which is mediated by this red stat gene >> which we discovered through studying these Tibetan the >> well no actually the red stat gene is something that's been discovered before this mutation was discovered the specific mutation of the gene >> and and we know that the the redstat gene does this which is it takes retinol and then it puts it into something called ATDR which is 1314 dihydro retinol. It's effectively an isomer type
1:14:57of thing where you take the retinol, you remove some double bonds, make them single bonds and things like that. And here we can see that the ATDR that ret the the rstat mediated >> thing that is coming out of the vitamin A that is going up. >> Okay. The concentration of this particular compound >> is going up because of this gene. >> Mhm. >> Yes. Okay. >> So, so we're we've now made the causal link >> between the presence of this gene mutation and >> now a specific compound >> compound this ATDR being present which we see in these spikes in that top section with the rest and Q24.
1:15:38>> Yeah. Yeah. And you can see that the second spike is larger than the control which means that you've got this is that gain of function that I was talking about, right? like this this particular mutation is giving me more ATDR and perhaps that more signal is telling the OPC's and the stem cells hey I need more myelin >> it's it's now loud enough when we have the because so actually this is a good point so the the in the three top charts right the second and third the rest and the rest Q24 that second the third one all the way to the right >> that's the that's the yak version >> that's the mutation >> and then the one in the middle is just like standard operating procedure And so potentially it's the unless the
1:16:18AT the ATDR being at a particular level might be >> the tipping point. And if it's below a particular level >> in hypoxia it might be a tipping point. Exactly. >> And perhaps in MS >> it might be a tipping point. >> Might be a tipping point. >> That's the connection we're trying to that's the bridge again from before that we're trying to >> Yeah. So okay, what if I just add ATDR,
Evolutionary BiologyNeurobiologyPharmacologyRegenerative Medicine