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?Knocking out Dicer in the brain!
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By RFZ, Section Wish list
Posted on Wed Apr 19th, 2006 at 01:18:04 PM PST
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This experiment is one that would yield a lot of results should it be feasible to carry out, which is why I thought I would post it. I'm sure there are labs that work on similar projects currently though excuse my ignorance, I cannot name them. Without more ado, here's the idea ;
to generate a model organism (mouse/rat) with a dicer knocked out in the brain to study miRNA regulation of gene expression
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The idea behind doing this is the knowledge that many varied genetic lesions are able to perturb normal brain function thus leading to mental illness. While microarrays and other technologies have been extensively employed to look at what is going wrong in the genes of diseased individuals, very little work has been done to explore post transcriptional gene regulation in the brain.
The extent of miRNA gene regulation is grabbing more and more attention in physiology. I propose that we study the global affects of possible miRNA gene expression in the brain by creating a tissue specific knock out dicer mouse.
To do this the dicer gene will have to be cloned, engineered with a brain specific promoter (cre-lox system or flip-frt) and then used to create a transgenic mouse (which is null for the normal Dicer gene of course). Once adult, a complete knock out of Dicer in the brain will have the result of knocking down all miRNA directed post transcriptional gene regulation. The effects of this screen could be quantified and qualified using the gamut of behavioral, biochemical and physiological tests in existence. By this we will be able to know what functions of the brain are dependant on miRNA regulation. I believe this knowledge will complement the existing data on genetic lesion driven mental illnesses and help us to refocus our attention on genetic mechanisms that are important to proper brain function
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