Water, MECP2, and Rett Syndrome
Could it be something in the water? The answer might seem “yes” if all you read is the headline of an article in today’s Scotsman:
Study reveals water’s role in rare autism
The water in question is not the wet stuff in oceans, lakes or rivers or in pools (where we’re shortly headed to—I told you Charlie liked swimming and I meant it!). It’s water at the molecular level, and is linked to Rett Sydrome, which has been linked to a mutation in the MECP2 gene:
Researchers discovered that Rett’s syndrome is caused by the Mecp2 protein interacting with water trapped around the DNA rather than reacting directly with the DNA itself.
Professor Adrian Bird [of University of Edinburgh], who took part in the study, said: “We thought this process involved oily components sticking together, but we didn’t expect oily contact to depend on water – because, of course, oil and water don’t mix.
“The discovery has enabled us to understand the reasons why the mutated proteins fail to function properly in Rett patients.”
Professor Bird’s lab is creating a mouse model of Rett Syndrome by targeted mutation of MECP2.
3 opinions for Water, MECP2, and Rett Syndrome
Regan
Jul 12, 2008 at 5:23 pm
For some reason I have this slight twinge in the back of my head that someone is going to skim this and think, “See, it IS the water”, and segue into some discussion of F- or such, based on some things I read on the web, vs. the mutation modifying the MECP2 structure.
(My understanding is that the only time when DNA is not hydrated is when it is chemically manipulated for such as X-ray diffraction, and the role of water is quite interesting because of its reactivity on its own merit in biologic process. If I have this incorrect I hope that someone will correct me.)
(Now I’m curious about what is modified in the MECP2.)
Kristina Chew, PhD
Jul 12, 2008 at 6:48 pm
@Regan, that was my thought (expressed in your first sentence) too—talk about a misleading headline to the article. When I looked up Prof. Bird’s lab, his research looks at methylation:
http://www.homepages.ed.ac.uk/dmac/Bird_Lab/birdlab.html
daedalus2u
Jul 12, 2008 at 8:03 pm
This is really a very misleading article.
Essentially everything in physiology is hydrated including DNA and all the proteins that interact with DNA. Hydrophobic parts of those proteins interact with lipid membranes. That is often how the proteins hold themselves in the right position in lipid membranes, the hydrophobic parts fit in the lipid and the hydrophilic parts in the aqueous part of the cell.
DNA methylation is the way that physiology “programs” DNA to behave in different ways in different cells. With DNA methylation, the same gene in a nerve cell can behave differently than the same gene in a liver cell, or a muscle cell, or a kidney cell, or any one of hundreds of cells.
MeCP2 is one of the proteins that “reads out” the different methylation patterns on those different genes.
There has been extremely sophisticated work on MeCP2 transgenic mice. Mice have been created which lose MeCP2 with a certain trigger, and then with a different trigger get it back. These mice recapitulate many many of the symptoms of Rett, They lose those symptoms when MeCP2 is turned back on.
Most cases of Rett are due to a deletion of MeCP2. It is on the X chromosome, which females have 2 of, and which are turned off at random, so in females with Rett some cells have an active MeCP2 gene and some don’t. Males only have a single X chromosome, and loss of MeCP2 is virtually always fatal in utero (which is why Rett in males is extremely rare).
Virtually all interactions can be modeled as a balance of hydrophilic and hydrophobic interactions. There is nothing surprising about this.
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